rs395357

chr17-3532786-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_145068.4(TRPV3):c.936G>A(p.Thr312=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,614,018 control chromosomes in the GnomAD database, including 179,737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14689 hom., cov: 33)
  • Exomes 𝑓: 0.47 (165048 hom.)
• Consequence: TRPV3 NM_145068.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.53

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-3532786-C-T is Benign according to our data. Variant chr17-3532786-C-T is described in ClinVar as [Benign]. Clinvar id is 322784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.53 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV3	NM_145068.4	c.936G>A	p.Thr312=	synonymous_variant	8/18	ENST00000576742.6
TRPV3	NM_001258205.2	c.936G>A	p.Thr312=	synonymous_variant	8/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV3	ENST00000576742.6	c.936G>A	p.Thr312=	synonymous_variant	8/18	1	NM_145068.4	P4

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65194 AN: 152044 Hom.: 14691 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.443

GnomAD3 exomes AF: 0.422 AC: 105997 AN: 251348 Hom.: 23812 AF XY: 0.429 AC XY: 58320 AN XY: 135838

Gnomad AFR exome AF: 0.340

Gnomad AMR exome AF: 0.237

Gnomad ASJ exome AF: 0.438

Gnomad EAS exome AF: 0.278

Gnomad SAS exome AF: 0.382

Gnomad FIN exome AF: 0.529

Gnomad NFE exome AF: 0.499

Gnomad OTH exome AF: 0.459

GnomAD4 exome AF: 0.470 AC: 686789 AN: 1461856 Hom.: 165048 Cov.: 84 AF XY: 0.468 AC XY: 340662 AN XY: 727226

Gnomad4 AFR exome AF: 0.327

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.445

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.383

Gnomad4 FIN exome AF: 0.522

Gnomad4 NFE exome AF: 0.496

Gnomad4 OTH exome AF: 0.452

GnomAD4 genome AF: 0.429 AC: 65223 AN: 152162 Hom.: 14689 Cov.: 33 AF XY: 0.429 AC XY: 31888 AN XY: 74382

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.441

Alfa AF: 0.483 Hom.: 35975

Bravo AF: 0.410

Asia WGS AF: 0.339 AC: 1182 AN: 3478

EpiCase AF: 0.507

EpiControl AF: 0.509

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	Genome-Nilou Lab	Sep 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 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	-0.83
Cadd	Benign	1.5
Dann	Benign	0.64

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: rs395357; hg19: chr17-3436080; COSMIC: COSV56789943; COSMIC: COSV56789943;