ClinVar Genomic variation as it relates to human health
NM_022114.4(PRDM16):c.3301G>A (p.Val1101Met)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_022114.4(PRDM16):c.3301G>A (p.Val1101Met)
Variation ID: 60727 Accession: VCV000060727.22
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p36.32 1: 3430888 (GRCh38) [ NCBI UCSC ] 1: 3347452 (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 Mar 5, 2016 Apr 15, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_022114.4:c.3301G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_071397.3:p.Val1101Met missense NM_199454.3:c.3301G>A NP_955533.2:p.Val1101Met missense NC_000001.11:g.3430888G>A NC_000001.10:g.3347452G>A NG_029576.2:g.366711G>A Q9HAZ2:p.Val1101Met - Protein change
- V1101M
- Other names
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- Canonical SPDI
- NC_000001.11:3430887:G:A
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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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0.00300 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00009
Trans-Omics for Precision Medicine (TOPMed) 0.00023
1000 Genomes Project 0.00300
The Genome Aggregation Database (gnomAD), exomes 0.00317
1000 Genomes Project 30x 0.00328
Exome Aggregation Consortium (ExAC) 0.00357
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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PRDM16 | - | - |
GRCh38 GRCh37 |
1253 | 1406 |
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 (1) |
no assertion criteria provided
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Jul 11, 2013 | RCV000054521.3 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Jan 31, 2024 | RCV000204421.12 | |
Benign (3) |
criteria provided, single submitter
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Apr 29, 2015 | RCV000223010.7 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV001610340.5 |
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. |
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Benign
(Apr 29, 2015)
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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: SCV000269733.3
First in ClinVar: May 29, 2016 Last updated: May 29, 2016 |
Comment:
p.Val1101Met in exon 15 of PRDM16: This variant is not expected to have clinical significance because it has been identified in 2.6% (422/16468) of South … (more)
p.Val1101Met in exon 15 of PRDM16: This variant is not expected to have clinical significance because it has been identified in 2.6% (422/16468) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs201654872). (less)
Number of individuals with the variant: 2
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Benign
(-)
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criteria provided, single submitter
Method: research
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Left ventricular noncompaction 8
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001435178.1
First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
Comment:
The heterozygous p.Val1101Met variant in PRDM16 has been identified in 2 individuals with dilated cardiomyopathy (PMID: 23768516), and has been identified in >2% of South … (more)
The heterozygous p.Val1101Met variant in PRDM16 has been identified in 2 individuals with dilated cardiomyopathy (PMID: 23768516), and has been identified in >2% of South Asian chromosomes and 7 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal dominant dilated cardiomyopathy. (less)
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Benign
(Oct 19, 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: SCV001842374.1
First in ClinVar: Sep 12, 2021 Last updated: Sep 12, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 27896284, 27535533, 24387995, 23768516)
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Left ventricular noncompaction 8
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000262005.9
First in ClinVar: Jan 31, 2016 Last updated: Feb 28, 2024 |
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Benign
(Feb 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: SCV004700755.2
First in ClinVar: Mar 10, 2024 Last updated: Apr 15, 2024 |
Comment:
PRDM16: BP4, BS1, BS2
Number of individuals with the variant: 1
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Uncertain significance
(Jul 11, 2013)
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no assertion criteria provided
Method: literature only
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RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000082999.3
First in ClinVar: Aug 23, 2013 Last updated: Mar 05, 2016 |
Comment on evidence:
This variant, formerly titled CARDIOMYOPATHY, DILATED, 1LL, has been reclassified based on the report of Lek et al. (2016). In 2 patients with dilated cardiomyopathy … (more)
This variant, formerly titled CARDIOMYOPATHY, DILATED, 1LL, has been reclassified based on the report of Lek et al. (2016). In 2 patients with dilated cardiomyopathy (CMD1LL; see 615373) who underwent heart transplantation, Arndt et al. (2013) identified heterozygosity for a c.3301G-A transition in exon 15 of the PRDM16 gene, resulting in a val1101-to-met (V1101M) substitution at a conserved residue in the C terminus, within a sequence that mediates interaction with SKI (164780) and regulation of TGFB (see 190180) signaling. Lek et al. (2016) noted that the V1101M variant has a high allele frequency (0.0256) in the South Asian population in the ExAC database, suggesting that it is not pathogenic. (less)
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001922166.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001929282.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001966590.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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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
HelpText-mined citations for rs201654872 ...
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.