VCV000031691.54 - ClinVar

NM_016042.4(EXOSC3):c.92G>C (p.Gly31Ala)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(22)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_016042.4(EXOSC3):c.92G>C (p.Gly31Ala)

Variation ID: 31691 Accession: VCV000031691.54

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 9p13.2 9: 37784953 (GRCh38) [ NCBI UCSC ] 9: 37784950 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 27, 2015	Oct 26, 2024	Mar 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_016042.4:c.92G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_057126.2:p.Gly31Ala	missense
NM_001002269.2:c.92G>C	NP_001002269.1:p.Gly31Ala	missense
NC_000009.12:g.37784953C>G
NC_000009.11:g.37784950C>G
NG_032780.1:g.5140G>C
	Q9NQT5:p.Gly31Ala

... more HGVS ... less HGVS

Protein change

G31A

Other names

Canonical SPDI

NC_000009.12:37784952:C:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.00000

Exome Aggregation Consortium (ExAC) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00002

Links

ClinGen: CA342800 UniProtKB: Q9NQT5#VAR_068505 OMIM: 606489.0004 dbSNP: rs387907196 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
EXOSC3		-	-	GRCh38 GRCh37	246	336

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Pontocerebellar hypoplasia type 1B	Pathogenic/Likely pathogenic (16)	criteria provided, multiple submitters, no conflicts	Aug 16, 2023	RCV000024369.42
Abnormal cerebellum morphology Fetal akinesia deformation sequence 1 Hypoplasia of the pons Lissencephaly Microcephaly Paucity of anterior horn motor neurons Severe intrauterine growth retardation	Pathogenic (1)	criteria provided, single submitter	Oct 9, 2019	RCV000853550.9
not provided	Pathogenic (4)	criteria provided, multiple submitters, no conflicts	May 2, 2022	RCV001092265.36
Congenital myopathy	Pathogenic (1)	criteria provided, single submitter	Mar 1, 2024	RCV004586024.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Aug 11, 2014)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Pontocerebellar hypoplasia, type 1B Affected status: yes Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000247330.1 First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015
Pathogenic (Oct 09, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Severe intrauterine growth retardation Fetal akinesia deformation sequence 1 Lissencephaly Microcephaly Abnormal cerebellum morphology Hypoplasia of the pons Paucity of anterior horn motor neurons (Autosomal recessive inheritance) Affected status: yes Allele origin: inherited	Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine Accession: SCV000995079.1 First in ClinVar: Nov 02, 2019 Last updated: Nov 02, 2019
Pathogenic (Nov 18, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics and Genomics, Karolinska University Hospital Accession: SCV001450345.1 First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020	Number of individuals with the variant: 1
Pathogenic (Jan 01, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Pontocerebellar hypoplasia type 1B Affected status: yes Allele origin: paternal	Provincial Medical Genetics Program of British Columbia, University of British Columbia Accession: SCV002496393.1 First in ClinVar: Apr 11, 2022 Last updated: Apr 11, 2022	Sex: female
Pathogenic (Jun 29, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Pontocerebellar hypoplasia type 1B Affected status: yes Allele origin: germline	MGZ Medical Genetics Center Accession: SCV002580899.1 First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 Comment: ACMG criteria applied: PS4, PM3, PS3_SUP, PM2_SUP, PP1, PP3	Number of individuals with the variant: 3 Sex: female
Pathogenic (Feb 16, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Pontocerebellar hypoplasia type 1B Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002810939.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Pathogenic (Jul 24, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Pontocerebellar hypoplasia type 1B Affected status: yes Allele origin: germline	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein Accession: SCV003807523.1 First in ClinVar: Mar 04, 2023 Last updated: Mar 04, 2023	Comment: ACMG classification criteria: PS3 supporting, PS4 strong, PM2 moderated, PM3 strong, PP1 strong, PP3 supporting Number of individuals with the variant: 1 Clinical Features: Primary Caesarian section (present) , Abnormal delivery (present) , Caesarian section (present) , Generalized hypotonia (present) , Global developmental delay (present) Geographic origin: Brazil Method: Paired-end whole-genome sequencing
Pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Pontocerebellar hypoplasia type 1B (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences Accession: SCV004227980.1 First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024	Publications: PubMed (2) PubMed: 22544365‚ 24524299 Comment: The p.(Gly31Ala) variant has a low general population frequency (G = 0.000020 in gnomAD) and it has not been found in the general Slovak population … (more) The p.(Gly31Ala) variant has a low general population frequency (G = 0.000020 in gnomAD) and it has not been found in the general Slovak population (PMID: 31054297). It is frequent in Czech Roma patients (the founder effect was suggested) and 4.4 % of unrelated Czech Roma control individuals were carriers (PMID: 23883322). Slovak patients show the same or highly similar haplotype, indicating a common origin (PMID: 35852507) (there has been a close connection between the Slovak and Czech populations). Interestingly, in the study PMID: 24524299 all patients who carried this variant were of Roma/Gypsy descent, although living in different countries (Sweden and Hungary) (a common founder?) (PMID: 23284067, PMID: 23883322). The variant is in the EXOSC3 N-terminal domain that is important for intersubunit interactions: residue Gly31 has been shown tightly packed against the surface of EXOSC5, indicating its importance for EXOSC3-EXOSC5 interactions (PMID: 29093021, PMID: 27777260). Patients homozygous for this variant manifest a severe disease course including death during infancy and hypoplasia of the pons (PMID: 24524299). (less) Number of individuals with the variant: 3 Family history: yes Secondary finding: no
Pathogenic (Feb 19, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Pontocerebellar hypoplasia type 1B Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV003823866.2 First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024
Pathogenic (Aug 16, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Pontocerebellar hypoplasia type 1B Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002238472.3 First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024	Publications: PubMed (3) PubMed: 22544365‚ 28053271‚ 30221345 Comment: For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects EXOSC3 function (PMID: 22544365, 28053271). This … (more) For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects EXOSC3 function (PMID: 22544365, 28053271). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 31 of the EXOSC3 protein (p.Gly31Ala). This variant is present in population databases (rs387907196, gnomAD 0.003%). This missense change has been observed in individuals with pontocerebellar hypoplasia (PMID: 22544365, 30221345). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 31691). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt EXOSC3 protein function. (less)
Pathogenic (Mar 01, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Congenital myopathy Affected status: yes Allele origin: germline	Muscle and Diseases Team, Institut de Génétique et Biologie Moléculaire et Cellulaire Accession: SCV005038553.1 First in ClinVar: Jul 15, 2024 Last updated: Jul 15, 2024	Publications: PubMed (1) PubMed: 30025162 DOI: 10.1186/s13073-024-01353-0 DOI: 10.1186/s13073-024-01353-0 Comment: PS1+PM1+PM2+PP2+PP3+PP4+PP5 Number of individuals with the variant: 1 Sex: male
Pathogenic (Nov 28, 2017)	criteria provided, single submitter (Classification criteria August 2017) Method: clinical testing	Pontocerebellar hypoplasia type 1B (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München Accession: SCV000680221.1 First in ClinVar: Feb 08, 2018 Last updated: Feb 08, 2018	Sex: female Tissue: blood
Pathogenic (Oct 23, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided (Unknown mechanism) Affected status: yes Allele origin: germline	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen Accession: SCV001447486.1 First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020	Clinical Features: Hypotonia (present) , Axial hypotonia (present) , Tongue fasciculations (present) Sex: male
Likely pathogenic (Feb 25, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Pontocerebellar hypoplasia type 1B Affected status: yes Allele origin: germline	Institute of Human Genetics, University Hospital Muenster Accession: SCV002499697.1 First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022	Comment: ACMG categories: PM2,PM3,PP3,PP5 Number of individuals with the variant: 1 Clinical Features: Global developmental delay (present) Age: 0-9 years Sex: male Tissue: blood
Pathogenic (May 02, 2022)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001801416.3 First in ClinVar: Aug 21, 2021 Last updated: Mar 04, 2023	Comment: Published yeast functional studies demonstrate a damaging effect with impaired pre-rRNA processing (Gillespie et al., 2017); Not observed at a significant frequency in large population … (more) Published yeast functional studies demonstrate a damaging effect with impaired pre-rRNA processing (Gillespie et al., 2017); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30986545, 27777260, 27876572, 23883322, 28053271, 29096039, 22544365, 30221345, 30025162, 29656927, 34426522, 31589614, 31770597, 24524299) (less)
Likely pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Pontocerebellar hypoplasia type 1B Affected status: yes Allele origin: unknown	3billion Accession: SCV004013766.1 First in ClinVar: Jul 22, 2023 Last updated: Jul 22, 2023	Publications: PubMed (1) PubMed: 22544365 Comment: The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). In silico tool predictions suggest damaging effect … (more) The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.74; 3Cnet: 0.81). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000031691 / PMID: 22544365). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 22544365). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. (less) Clinical Features: Generalized hypotonia (present) , Areflexia (present) , Hip contracture (present) , Elbow flexion contracture (present) , Ankle flexion contracture (present) , Knee flexion contracture (present) … (more) Generalized hypotonia (present) , Areflexia (present) , Hip contracture (present) , Elbow flexion contracture (present) , Ankle flexion contracture (present) , Knee flexion contracture (present) , Abnormal facial shape (present) (less)
Pathogenic (Jan 01, 2020)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001248685.26 First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024	Number of individuals with the variant: 3
Pathogenic (Dec 01, 2013)	no assertion criteria provided Method: literature only	PONTOCEREBELLAR HYPOPLASIA, TYPE 1B Affected status: not provided Allele origin: germline	OMIM Accession: SCV000045662.3 First in ClinVar: Apr 04, 2013 Last updated: Feb 27, 2015	Publications: PubMed (2) PubMed: 22544365‚ 23883322 Comment on evidence: In 2 Czech sibs with pontocerebellar hypoplasia type 1B (PCH1B; 614678), Wan et al. (2012) identified compound heterozygosity for 2 mutations in the EXOSC3 gene: … (more) In 2 Czech sibs with pontocerebellar hypoplasia type 1B (PCH1B; 614678), Wan et al. (2012) identified compound heterozygosity for 2 mutations in the EXOSC3 gene: a 92G-C transversion in exon 1, resulting in a gly31-to-ala (G31A) substitution at a highly conserved residue in the N-terminal domain, and a 712T-C transition in exon 4, resulting in a trp238-to-arg (W238R; 606489.0005) substitution at a highly conserved residue in the putative RNA-binding KH domain. Another unrelated Czech boy with the disorder was homozygous for the G31A mutation. Neither mutation was found in 379 control individuals. Schwabova et al. (2013) identified a homozygous G31A mutation in 2 unrelated Czech children of Roma descent with PCH1B. The heterozygous mutation was found in 4 (4.4%) of 90 unrelated Roma control individuals, and haplotype analysis suggested a founder effect. The patients had a severe form of the disorder, with death in the first year of life. (less)
Likely pathogenic (Jun 01, 2022)	no assertion criteria provided Method: provider interpretation	Pontocerebellar hypoplasia type 1B Affected status: yes Allele origin: inherited	Solve-RD Consortium Accession: SCV005091396.1 First in ClinVar: Oct 26, 2024 Last updated: Oct 26, 2024 Comment: Variant identified during reanalysis of unsolved cases by the Solve-RD project. The Solve-RD project has received funding from the European Union’s Horizon 2020 research and … (more) Variant identified during reanalysis of unsolved cases by the Solve-RD project. The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 779257. (less)	Comment: Variant confirmed as disease-causing by referring clinical team
Likely pathogenic (-)	no assertion criteria provided (ACGS Guidelines, 2016) Method: clinical testing	Pontocerebellar hypoplasia type 1B Affected status: yes Allele origin: germline	Genomics England Pilot Project, Genomics England Accession: SCV001760238.1 First in ClinVar: Jul 31, 2021 Last updated: Jul 31, 2021
Pathogenic (Nov 02, 2021)	no assertion criteria provided Method: clinical testing	Pontocerebellar hypoplasia type 1B Affected status: yes Allele origin: germline	Clinical Genetics Laboratory, University Hospital Schleswig-Holstein Accession: SCV002583327.1 First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
not provided (-)	no classification provided Method: literature only	Pontocerebellar hypoplasia type 1B Affected status: yes Allele origin: germline	GeneReviews Accession: SCV000189383.2 First in ClinVar: Oct 11, 2015 Last updated: Oct 01, 2022	Publications: BookShelf: NBK236968 BookShelf: NBK236968 Ethnicity/Population group: Prevalent among the Roma population.
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Comment:

The p.(Gly31Ala) variant has a low general population frequency (G = 0.000020 in gnomAD) and it has not been found in the general Slovak population (PMID: 31054297). It is frequent in Czech Roma patients (the founder effect was suggested) and 4.4 % of unrelated Czech Roma control individuals were carriers (PMID: 23883322). Slovak patients show the same or highly similar haplotype, indicating a common origin (PMID: 35852507) (there has been a close connection between the Slovak and Czech populations). Interestingly, in the study PMID: 24524299 all patients who carried this variant were of Roma/Gypsy descent, although living in different countries (Sweden and Hungary) (a common founder?) (PMID: 23284067, PMID: 23883322). The variant is in the EXOSC3 N-terminal domain that is important for intersubunit interactions: residue Gly31 has been shown tightly packed against the surface of EXOSC5, indicating its importance for EXOSC3-EXOSC5 interactions (PMID: 29093021, PMID: 27777260). Patients homozygous for this variant manifest a severe disease course including death during infancy and hypoplasia of the pons (PMID: 24524299).

Comment:

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects EXOSC3 function (PMID: 22544365, 28053271). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 31 of the EXOSC3 protein (p.Gly31Ala). This variant is present in population databases (rs387907196, gnomAD 0.003%). This missense change has been observed in individuals with pontocerebellar hypoplasia (PMID: 22544365, 30221345). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 31691). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt EXOSC3 protein function.

Comment:

Published yeast functional studies demonstrate a damaging effect with impaired pre-rRNA processing (Gillespie et al., 2017); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30986545, 27777260, 27876572, 23883322, 28053271, 29096039, 22544365, 30221345, 30025162, 29656927, 34426522, 31589614, 31770597, 24524299)

Comment:

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.74; 3Cnet: 0.81). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000031691 / PMID: 22544365). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 22544365). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Exome sequencing in undiagnosed congenital myopathy reveals new genes and refines genes-phenotypes correlations.	de Feraudy Y	Genome medicine	2024	DOI: 10.1186/s13073-024-01353-0
EXOSC3 Pontocerebellar Hypoplasia.	Adam MP	-	2020	PMID: 25144110
Sarcomeric disorganization and nemaline bodies in muscle biopsies of patients with EXOSC3-related type 1 pontocerebellar hypoplasia.	Pinto MM	Muscle & nerve	2019	PMID: 30025162
Genomic screening in rare disorders: New mutations and phenotypes, highlighting ALG14 as a novel cause of severe intellectual disability.	Kvarnung M	Clinical genetics	2018	PMID: 30221345
Mutations of EXOSC3/Rrp40p associated with neurological diseases impact ribosomal RNA processing functions of the exosome in S. cerevisiae.	Gillespie A	RNA (New York, N.Y.)	2017	PMID: 28053271
EXOSC3 mutations in pontocerebellar hypoplasia type 1: novel mutations and genotype-phenotype correlations.	Eggens VR	Orphanet journal of rare diseases	2014	PMID: 24524299
Homozygous EXOSC3 mutation c.92G→C, p.G31A is a founder mutation causing severe pontocerebellar hypoplasia type 1 among the Czech Roma.	Schwabova J	Journal of neurogenetics	2013	PMID: 23883322
Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration.	Wan J	Nature genetics	2012	PMID: 22544365

Text-mined citations for rs387907196 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 27, 2024

ClinVar Genomic variation as it relates to human health

NM_016042.4(EXOSC3):c.92G>C (p.Gly31Ala)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs387907196 ...