17-3518738-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_145068.4(TRPV3):c.1923C>T(p.Asp641Asp) 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

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.72

Publications

20 publications found

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 Gene-Disease associations (from GenCC):

mutilating palmoplantar keratoderma with periorificial keratotic plaques
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet
Olmsted syndrome 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
isolated focal non-epidermolytic palmoplantar keratoderma
Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

TRPV3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 322758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
TRPV3	NM_145068.4 link	c.1923C>T	p.Asp641Asp	synonymous_variant	Exon 15 of 18	ENST00000576742.6	NP_659505.1	Q8NET8-1
TRPV3	NM_001258205.2 link	c.1923C>T	p.Asp641Asp	synonymous_variant	Exon 15 of 18		NP_001245134.1	B2KYM6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV3	ENST00000576742.6 link	c.1923C>T	p.Asp641Asp	synonymous_variant	Exon 15 of 18	1	NM_145068.4	ENSP00000461518.2		Q8NET8-1

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84517

AN:

151948

Hom.:

24150

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.590

AC:

147308

AN:

249626

AF XY:

0.593

show subpopulations

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 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.:

AF XY:

0.546

AC XY:

396572

AN XY:

726626

show subpopulations

African (AFR)

AF:

0.554

AC:

18536

AN:

33472

American (AMR)

AF:

0.633

AC:

28178

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.597

AC:

15581

AN:

26106

East Asian (EAS)

AF:

0.959

AC:

38057

AN:

39686

South Asian (SAS)

AF:

0.695

AC:

59878

AN:

86126

European-Finnish (FIN)

AF:

0.468

AC:

24940

AN:

53346

Middle Eastern (MID)

AF:

0.606

AC:

3495

AN:

5766

European-Non Finnish (NFE)

AF:

0.511

AC:

567501

AN:

1111448

Other (OTH)

AF:

0.566

AC:

34175

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

21068

42136

63203

84271

105339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16672

33344

50016

66688

83360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.556

AC:

84581

AN:

152066

Hom.:

24167

Cov.:

AF XY:

0.559

AC XY:

41573

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.554

AC:

22995

AN:

41480

American (AMR)

AF:

0.610

AC:

9330

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.598

AC:

2073

AN:

3466

East Asian (EAS)

AF:

0.951

AC:

4923

AN:

5176

South Asian (SAS)

AF:

0.721

AC:

3479

AN:

4826

European-Finnish (FIN)

AF:

0.451

AC:

4766

AN:

10568

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.515

AC:

34960

AN:

67940

Other (OTH)

AF:

0.623

AC:

1316

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1906

3813

5719

7626

9532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

730

1460

2190

2920

3650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.534

Hom.:

17632

Bravo

AF:

0.570

Asia WGS

AF:

0.812

AC:

2825

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

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

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Isolated focal non-epidermolytic palmoplantar keratoderma

Benign:2

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. -

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.41

CADD

Benign

7.2

(source)

DANN

Benign

0.78

PhyloP100

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over