ClinVar Genomic variation as it relates to human health
NM_181503.3(EXOSC8):c.815G>C (p.Ser272Thr)
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.
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.
Likely pathogenic(1); Uncertain significance(2); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_181503.3(EXOSC8):c.815G>C (p.Ser272Thr)
Variation ID: 157608 Accession: VCV000157608.34
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q13.3 13: 37009283 (GRCh38) [ NCBI UCSC ] 13: 37583420 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Oct 11, 2015 Apr 15, 2024 Mar 25, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_181503.3:c.815G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_852480.1:p.Ser272Thr missense NC_000013.11:g.37009283G>C NC_000013.10:g.37583420G>C NG_042275.1:g.13743G>C Q96B26:p.Ser272Thr - Protein change
- S272T
- Other names
- -
- Canonical SPDI
- NC_000013.11:37009282:G:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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0.00220 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00220
1000 Genomes Project 30x 0.00234
Trans-Omics for Precision Medicine (TOPMed) 0.00367
The Genome Aggregation Database (gnomAD), exomes 0.00385
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00400
The Genome Aggregation Database (gnomAD) 0.00400
Exome Aggregation Consortium (ExAC) 0.00403
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 | ||
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HI score
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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. |
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EXOSC8 | - | - |
GRCh38 GRCh37 |
89 | 145 |
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. |
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Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
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Mar 25, 2024 | RCV000144941.8 | |
Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Mar 1, 2024 | RCV000418794.26 |
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. |
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Uncertain significance
(Jan 24, 2019)
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criteria provided, single submitter
Method: clinical testing
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Pontocerebellar hypoplasia, type 1C
Affected status: yes
Allele origin:
paternal
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Baylor Genetics
Accession: SCV001520007.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
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Likely benign
(Mar 06, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000617862.1
First in ClinVar: Dec 19, 2017 Last updated: Dec 19, 2017 |
Comment:
This variant is associated with the following publications: (PMID: 27127732, 24989451, 29431110, 30581635, 29758258, 29093021, 31664448, 31980526)
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Uncertain significance
(Mar 25, 2024)
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criteria provided, single submitter
Method: research
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Pontocerebellar hypoplasia, type 1C
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004805570.2
First in ClinVar: Mar 30, 2024 Last updated: Apr 06, 2024 |
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Likely benign
(Mar 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001149006.21
First in ClinVar: Feb 03, 2020 Last updated: Apr 15, 2024 |
Comment:
EXOSC8: BS2
Number of individuals with the variant: 10
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Likely pathogenic
(Feb 07, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000511780.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely benign
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001119618.4
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
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Pathogenic
(Jul 03, 2014)
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no assertion criteria provided
Method: literature only
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PONTOCEREBELLAR HYPOPLASIA, TYPE 1C
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000191958.2
First in ClinVar: Nov 15, 2014 Last updated: Oct 11, 2015 |
Comment on evidence:
In 10 affected individuals from 2 unrelated consanguineous Hungarian Roma families with pontocerebellar hypoplasia type 1C (PCH1C; 616081), Boczonadi et al. (2014) identified a homozygous … (more)
In 10 affected individuals from 2 unrelated consanguineous Hungarian Roma families with pontocerebellar hypoplasia type 1C (PCH1C; 616081), Boczonadi et al. (2014) identified a homozygous c.815G-C transversion in the EXOSC8 gene, resulting in a ser272-to-thr (S272T) substitution at a highly conserved residue. The mutation, which was found using a combination of homozygosity mapping and exome sequencing, segregated with the disorder in the families. The mutation was filtered against the 1000 Genomes Project and Exome Sequencing Project databases, as well as 334 in-house control exomes. The c.815G-C mutation was found at a frequency of 3% in the general Roma population, consistent with a founder effect. Patient cells showed significantly decreased EXOSC8 protein levels. (less)
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not provided
(-)
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no classification provided
Method: phenotyping only
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Pontocerebellar hypoplasia, type 1c
Affected status: unknown
Allele origin:
maternal
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GenomeConnect, ClinGen
Accession: SCV000840340.1
First in ClinVar: Oct 13, 2018 Last updated: Oct 13, 2018 |
Comment:
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical … (more)
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Abnormality of the umbilical cord (present) , Premature birth (present) , Abnormality of the placenta (present) , Prenatal maternal abnormality (present) , Abnormal delivery (present) … (more)
Abnormality of the umbilical cord (present) , Premature birth (present) , Abnormality of the placenta (present) , Prenatal maternal abnormality (present) , Abnormal delivery (present) , Abnormality of the amniotic fluid (present) , Oral-pharyngeal dysphagia (present) , Abnormality of the skull (present) , Abnormality of the hair (present) , Abnormality of vision (present) , Abnormality of eye movement (present) , Seizures (present) , Encephalopathy (present) , EEG abnormality (present) , Abnormality of coordination (present) , Cognitive impairment (present) , Cerebral palsy (present) , Morphological abnormality of the central nervous system (present) , Generalized hypotonia (present) , Hypertonia (present) , Abnormality of the musculature of the pelvis (present) , Abnormality of the musculature of the limbs (present) , Abnormality of muscle physiology (present) , Decreased pulmonary function (present) , Abnormality of the lung (present) , Gastrointestinal dysmotility (present) , Abnormality of the stomach (present) , Feeding difficulties (present) (less)
Indication for testing: Diagnostic
Age: 0-9 years
Sex: female
Testing laboratory: GeneDx
Date variant was reported to submitter: 2017-07-18
Testing laboratory interpretation: Uncertain significance
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia. | Boczonadi V | Nature communications | 2014 | PMID: 24989451 |
Text-mined citations for rs36027220 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.