rs1039519

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_145068.4(TRPV3):c.270G>A(p.Gln90Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,607,082 control chromosomes in the GnomAD database, including 304,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27948 hom., cov: 31)

Exomes 𝑓: 0.61 ( 276357 hom. )

Consequence

TRPV3
NM_145068.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.882

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 17-3544620-C-T is Benign according to our data. Variant chr17-3544620-C-T is described in ClinVar as [Benign]. Clinvar id is 322795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-3544620-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.882 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV3	NM_145068.4 link	c.270G>A	p.Gln90Gln	synonymous_variant	Exon 4 of 18	ENST00000576742.6	NP_659505.1	Q8NET8-1
TRPV3	NM_001258205.2 link	c.270G>A	p.Gln90Gln	synonymous_variant	Exon 4 of 18		NP_001245134.1	B2KYM6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV3	ENST00000576742.6 link	c.270G>A	p.Gln90Gln	synonymous_variant	Exon 4 of 18	1	NM_145068.4	ENSP00000461518.2		Q8NET8-1

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

91504

AN:

151822

Hom.:

27926

Cov.:

show subpopulations

Gnomad AFR

AF:

0.561

Gnomad AMI

AF:

0.564

Gnomad AMR

AF:

0.690

Gnomad ASJ

AF:

0.682

Gnomad EAS

AF:

0.789

Gnomad SAS

AF:

0.701

Gnomad FIN

AF:

0.573

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.588

Gnomad OTH

AF:

0.602

GnomAD3 exomes

AF:

0.644

AC:

156912

AN:

243626

Hom.:

51828

AF XY:

0.641

AC XY:

84590

AN XY:

131906

show subpopulations

Gnomad AFR exome

AF:

0.555

Gnomad AMR exome

AF:

0.798

Gnomad ASJ exome

AF:

0.678

Gnomad EAS exome

AF:

0.782

Gnomad SAS exome

AF:

0.702

Gnomad FIN exome

AF:

0.568

Gnomad NFE exome

AF:

0.584

Gnomad OTH exome

AF:

0.624

GnomAD4 exome

AF:

0.613

AC:

891497

AN:

1455142

Hom.:

276357

Cov.:

AF XY:

0.615

AC XY:

444860

AN XY:

723756

show subpopulations

Gnomad4 AFR exome

AF:

0.553

Gnomad4 AMR exome

AF:

0.789

Gnomad4 ASJ exome

AF:

0.680

Gnomad4 EAS exome

AF:

0.803

Gnomad4 SAS exome

AF:

0.705

Gnomad4 FIN exome

AF:

0.573

Gnomad4 NFE exome

AF:

0.593

Gnomad4 OTH exome

AF:

0.626

GnomAD4 genome

AF:

0.603

AC:

91580

AN:

151940

Hom.:

27948

Cov.:

AF XY:

0.606

AC XY:

44962

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.562

Gnomad4 AMR

AF:

0.691

Gnomad4 ASJ

AF:

0.682

Gnomad4 EAS

AF:

0.788

Gnomad4 SAS

AF:

0.702

Gnomad4 FIN

AF:

0.573

Gnomad4 NFE

AF:

0.588

Gnomad4 OTH

AF:

0.605

Alfa

AF:

0.598

Hom.:

39215

Bravo

AF:

0.611

Asia WGS

AF:

0.700

AC:

2436

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Isolated focal non-epidermolytic palmoplantar keratoderma

Benign:2

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.2

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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