VCV000010981.4 - ClinVar

NM_001032382.2(PQBP1):c.461_462del (p.Glu154fs)

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.

(2)

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

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001032382.2(PQBP1):c.461_462del (p.Glu154fs)

Variation ID: 10981 Accession: VCV000010981.4

Type and length

Microsatellite, 2 bp

Location

Cytogenetic: Xp11.23 X: 48902391-48902392 (GRCh38) [ NCBI UCSC ] X: 48759668-48759669 (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	Apr 4, 2013	Jan 4, 2020	Feb 28, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NM_001032382.2:c.461_462del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001027554.1:p.Glu154fs	frameshift
NM_001032381.2:c.461_462del	NP_001027553.1:p.Glu154fs	frameshift
NM_001032383.1:c.461_462del
NM_001032383.2:c.461_462del	NP_001027555.1:p.Glu154fs	frameshift
NM_001032384.1:c.461_462del	NP_001027556.1:p.Glu154fs	frameshift
NM_001167989.2:c.461_462del	NP_001161461.1:p.Glu154fs	frameshift
NM_001167990.2:c.437_438del	NP_001161462.1:p.Glu146fs	frameshift
NM_001167992.1:c.202-51AG[5]		intron variant
NM_005710.2:c.461_462del	NP_005701.1:p.Glu154fs	frameshift
NM_144495.3:c.293-341AG[5]		intron variant
NC_000023.11:g.48902391AG[5]
NC_000023.10:g.48759668AG[5]
NG_015967.1:g.9474AG[5]
NG_015968.2:g.748CT[5]
NG_034300.1:g.14557CT[5]

... more HGVS ... less HGVS

Protein change

E154fs, E146fs

Other names

Canonical SPDI

NC_000023.11:48902390:AGAGAGAGAGAG:AGAGAGAGAG

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.

Links

ClinGen: CA121284 OMIM: 300463.0003 dbSNP: rs606231193 VarSome

Comment on variant

NCBI staff reviewed the sequence information reported in PubMed 14634649 Fig. 1 to determine the location of this allele on the current reference sequence.

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.
PQBP1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	144	332

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.
Renpenning syndrome	Pathogenic (2)	no assertion criteria provided	Feb 28, 2019	RCV000011728.5

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 (Jan 01, 2007)	no assertion criteria provided Method: literature only	RENPENNING SYNDROME Affected status: not provided Allele origin: germline	OMIM Accession: SCV000031960.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Publications: PubMed (4) PubMed: 7943045‚ 14634649‚ 15024694‚ 17033686 Comment on evidence: In affected males from a family with an X-linked mental retardation syndrome (309500) reported by Hamel et al. (1994), Kalscheuer et al. (2003) identified a … (more) In affected males from a family with an X-linked mental retardation syndrome (309500) reported by Hamel et al. (1994), Kalscheuer et al. (2003) identified a deletion of a single AG dinucleotide at position 3898 in the PQBP1 gene. All affected males had congenital heart defects in addition to severe mental retardation, microcephaly, spasticity, short stature, cleft or highly arched palate, and other craniofacial abnormalities. The mother of 2 of the affected individuals had a corrected atrial septal defect. Facial features coarsened with age. Lenski et al. (2004) referred to this as the cerebropalatocardiac syndrome or Hamel syndrome. In 2 male cousins with right microphthalmia and left choroid coloboma, microcephaly, mental retardation, renal hypoplasia, and spastic diplegia, Martinez-Garay et al. (2007) identified a 2-bp deletion in the PQBP1 gene that they designated 461delAG; they stated that it was the same deletion previously reported by Kalscheuer et al. (2003). The deletion was also found in both obligate carrier mothers; haplotype analysis suggested germline mosaicism for the deletion in the maternal grandmother. (less)
Pathogenic (Feb 28, 2019)	no assertion criteria provided Method: provider interpretation	Renpenning syndrome 1 Affected status: yes Allele origin: germline	Codex Genetics Limited Accession: SCV000996000.1 First in ClinVar: Jan 04, 2020 Last updated: Jan 04, 2020	Publications: PubMed (4) PubMed: 17033686‚ 15024694‚ 14634649‚ 7943045 Age: 60-69 years Sex: male

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

Title	Author	Journal	Year	Link
A two base pair deletion in the PQBP1 gene is associated with microphthalmia, microcephaly, and mental retardation.	Martínez-Garay I	European journal of human genetics : EJHG	2007	PMID: 17033686
Novel truncating mutations in the polyglutamine tract binding protein 1 gene (PQBP1) cause Renpenning syndrome and X-linked mental retardation in another family with microcephaly.	Lenski C	American journal of human genetics	2004	PMID: 15024694
Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation.	Kalscheuer VM	Nature genetics	2003	PMID: 14634649
Mental retardation, congenital heart defect, cleft palate, short stature, and facial anomalies: a new X-linked multiple congenital anomalies/mental retardation syndrome: clinical description and molecular studies.	Hamel BC	American journal of medical genetics	1994	PMID: 7943045

Text-mined citations for rs606231193 ...

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 Apr 25, 2022

ClinVar Genomic variation as it relates to human health

NM_001032382.2(PQBP1):c.461_462del (p.Glu154fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs606231193 ...