rs7216486
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_145068.4(TRPV3):c.1923C>T(p.Asp641=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,612,890 control chromosomes in the GnomAD database, including 244,216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.56 ( 24167 hom., cov: 32)
Exomes 𝑓: 0.54 ( 220049 hom. )
Consequence
TRPV3
NM_145068.4 synonymous
NM_145068.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.72
Genes affected
TRPV3 (HGNC:18084): (transient receptor potential cation channel subfamily V member 3) This gene product belongs to a family of nonselective cation channels that function in a variety of processes, including temperature sensation and vasoregulation. The thermosensitive members of this family are expressed in subsets of sensory neurons that terminate in the skin, and are activated at distinct physiological temperatures. This channel is activated at temperatures between 22 and 40 degrees C. This gene lies in close proximity to another family member gene on chromosome 17, and the two encoded proteins are thought to associate with each other to form heteromeric channels. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 17-3518738-G-A is Benign according to our data. Variant chr17-3518738-G-A is described in ClinVar as [Benign]. Clinvar id is 322758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-3518738-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=1.72 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPV3 | NM_145068.4 | c.1923C>T | p.Asp641= | synonymous_variant | 15/18 | ENST00000576742.6 | |
TRPV3 | NM_001258205.2 | c.1923C>T | p.Asp641= | synonymous_variant | 15/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPV3 | ENST00000576742.6 | c.1923C>T | p.Asp641= | synonymous_variant | 15/18 | 1 | NM_145068.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.556 AC: 84517AN: 151948Hom.: 24150 Cov.: 32
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GnomAD3 exomes AF: 0.590 AC: 147308AN: 249626Hom.: 45552 AF XY: 0.593 AC XY: 79922AN XY: 134866
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GnomAD4 exome AF: 0.541 AC: 790341AN: 1460824Hom.: 220049 Cov.: 63 AF XY: 0.546 AC XY: 396572AN XY: 726626
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GnomAD4 genome AF: 0.556 AC: 84581AN: 152066Hom.: 24167 Cov.: 32 AF XY: 0.559 AC XY: 41573AN XY: 74342
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Isolated focal non-epidermolytic palmoplantar keratoderma Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Olmsted syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at