rs7216486

chr17-3518738-G-Achr17-3518738-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• 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]

ACMG classification

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: 84517 AN: 151948 Hom.: 24150 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.618

GnomAD3 exomes AF: 0.590 AC: 147308 AN: 249626 Hom.: 45552 AF XY: 0.593 AC XY: 79922 AN XY: 134866

Gnomad AFR exome AF: 0.549

Gnomad AMR exome AF: 0.630

Gnomad ASJ exome AF: 0.601

Gnomad EAS exome AF: 0.953

Gnomad SAS exome AF: 0.695

Gnomad FIN exome AF: 0.457

Gnomad NFE exome AF: 0.522

Gnomad OTH exome AF: 0.581

GnomAD4 exome AF: 0.541 AC: 790341 AN: 1460824 Hom.: 220049 Cov.: 63 AF XY: 0.546 AC XY: 396572 AN XY: 726626

Gnomad4 AFR exome AF: 0.554

Gnomad4 AMR exome AF: 0.633

Gnomad4 ASJ exome AF: 0.597

Gnomad4 EAS exome AF: 0.959

Gnomad4 SAS exome AF: 0.695

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.511

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.556 AC: 84581 AN: 152066 Hom.: 24167 Cov.: 32 AF XY: 0.559 AC XY: 41573 AN XY: 74342

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.951

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.623

Alfa AF: 0.534 Hom.: 15852

Bravo AF: 0.570

Asia WGS AF: 0.812 AC: 2825 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Isolated focal non-epidermolytic palmoplantar keratoderma Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Olmsted syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	7.2
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7216486; hg19: chr17-3422032; COSMIC: COSV56791501; COSMIC: COSV56791501;