ClinVar Genomic variation as it relates to human health
NM_001384140.1(PCDH15):c.949T>A (p.Ser317Thr)
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.
Uncertain significance(5); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001384140.1(PCDH15):c.949T>A (p.Ser317Thr)
Variation ID: 96235 Accession: VCV000096235.28
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q21.1 10: 54236859 (GRCh38) [ NCBI UCSC ] 10: 55996619 (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 Dec 6, 2016 Feb 14, 2024 Jan 15, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001384140.1:c.949T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001371069.1:p.Ser317Thr missense NM_033056.4:c.949T>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_149045.3:p.Ser317Thr missense NM_001142763.2:c.964T>A NP_001136235.1:p.Ser322Thr missense NM_001142764.2:c.949T>A NP_001136236.1:p.Ser317Thr missense NM_001142765.2:c.949T>A NP_001136237.1:p.Ser317Thr missense NM_001142766.2:c.949T>A NP_001136238.1:p.Ser317Thr missense NM_001142767.2:c.838T>A NP_001136239.1:p.Ser280Thr missense NM_001142768.2:c.883T>A NP_001136240.1:p.Ser295Thr missense NM_001142769.3:c.964T>A NP_001136241.1:p.Ser322Thr missense NM_001142770.3:c.949T>A NP_001136242.1:p.Ser317Thr missense NM_001142771.2:c.964T>A NP_001136243.1:p.Ser322Thr missense NM_001142772.2:c.949T>A NP_001136244.1:p.Ser317Thr missense NM_001142773.2:c.883T>A NP_001136245.1:p.Ser295Thr missense NM_001354404.2:c.883T>A NP_001341333.1:p.Ser295Thr missense NM_001354411.2:c.949T>A NP_001341340.1:p.Ser317Thr missense NM_001354420.2:c.949T>A NP_001341349.1:p.Ser317Thr missense NM_001354429.2:c.949T>A NP_001341358.1:p.Ser317Thr missense NM_001354430.2:c.949T>A NP_001341359.1:p.Ser317Thr missense NC_000010.11:g.54236859A>T NC_000010.10:g.55996619A>T NG_009191.3:g.1397324T>A - Protein change
- S317T, S295T, S280T, S322T
- Other names
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- Canonical SPDI
- NC_000010.11:54236858:A:T
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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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0.00120 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00172
The Genome Aggregation Database (gnomAD), exomes 0.00019
The Genome Aggregation Database (gnomAD) 0.00085
1000 Genomes Project 0.00120
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00077
Exome Aggregation Consortium (ExAC) 0.00026
Trans-Omics for Precision Medicine (TOPMed) 0.00106
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
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. |
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PCDH15 | - | - |
GRCh38 GRCh37 |
3320 | 3407 |
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 (2) |
criteria provided, multiple submitters, no conflicts
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Jan 3, 2019 | RCV000082317.26 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jan 15, 2024 | RCV000657972.23 | |
Uncertain significance (1) |
criteria provided, single submitter
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Oct 8, 2019 | RCV001804834.9 |
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
(Nov 11, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000604606.1
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Uncertain significance
(Oct 09, 2015)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000114274.8
First in ClinVar: Jan 17, 2014 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Uncertain significance
(Jan 12, 2018)
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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: SCV000779743.2
First in ClinVar: Jul 09, 2018 Last updated: Dec 15, 2018 |
Comment:
The S317T variant in the PCDH15 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The … (more)
The S317T variant in the PCDH15 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The S317T variant is observed in 60/277126 (0.022%) alleles in large population cohorts, with no homozygotes observed (Lek et al., 2016). The S317T variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret S317T as a variant of uncertain significance. (less)
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Uncertain significance
(Jan 03, 2019)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000711191.2
First in ClinVar: Apr 09, 2018 Last updated: Aug 26, 2019 |
Comment:
The p.Ser317Thr variant in PCDH15 has been previously reported by our laboratory in 1 individuals with hearing loss, and was also identified in 0.24% (60/24968) … (more)
The p.Ser317Thr variant in PCDH15 has been previously reported by our laboratory in 1 individuals with hearing loss, and was also identified in 0.24% (60/24968) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org). This varia nt has also been reported in ClinVar (Variation iD 96235). Computational predict ion tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Ser317 Thr variant is uncertain. ACMG/AMP Criteria applied: BS1_Supporting. (less)
Number of individuals with the variant: 2
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Uncertain significance
(Oct 08, 2019)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 23
Affected status: yes
Allele origin:
maternal
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Center of Genomic medicine, Geneva, University Hospital of Geneva
Accession: SCV001745854.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
Comment:
Two variants in this gene (PCDH15) were found to be in cis (both were inherited form the mother) in a young male with postlingual bilateral … (more)
Two variants in this gene (PCDH15) were found to be in cis (both were inherited form the mother) in a young male with postlingual bilateral severe hearing loss (less)
Number of individuals with the variant: 1
Age: 10-19 years
Sex: male
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Likely benign
(Jan 15, 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: SCV001050367.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024 |
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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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http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PCDH15 | - | - | - | - |
Text-mined citations for rs140736502 ...
HelpRecord last updated Apr 20, 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.