rs395357

Positions:

chr17-3532786-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.53

Variant links:

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]

TRPV3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
TRPV3	NM_145068.4 linkuse as main transcript	c.936G>A	p.Thr312=	synonymous_variant	8/18	ENST00000576742.6	NP_659505.1
TRPV3	NM_001258205.2 linkuse as main transcript	c.936G>A	p.Thr312=	synonymous_variant	8/18		NP_001245134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV3	ENST00000576742.6 linkuse as main transcript	c.936G>A	p.Thr312=	synonymous_variant	8/18	1	NM_145068.4	ENSP00000461518	P4	Q8NET8-1

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65194

AN:

152044

Hom.:

14691

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.468

AC XY:

340662

AN XY:

727226

show subpopulations

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.:

AF XY:

0.429

AC XY:

31888

AN XY:

74382

show subpopulations

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:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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. -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over