17-3532786-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_145068.4(TRPV3):c.936G>A(p.Thr312Thr) 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

Publications

26 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 -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 VariationId 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 rank	MANE	Protein	UniProt
TRPV3	NM_145068.4 link	c.936G>A	p.Thr312Thr	synonymous_variant	Exon 8 of 18	ENST00000576742.6	NP_659505.1	Q8NET8-1
TRPV3	NM_001258205.2 link	c.936G>A	p.Thr312Thr	synonymous_variant	Exon 8 of 18		NP_001245134.1	B2KYM6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV3	ENST00000576742.6 link	c.936G>A	p.Thr312Thr	synonymous_variant	Exon 8 of 18	1	NM_145068.4	ENSP00000461518.2		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

GnomAD2 exomes

AF:

0.422

AC:

105997

AN:

251348

AF XY:

0.429

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 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

African (AFR)

AF:

0.327

AC:

10938

AN:

33476

American (AMR)

AF:

0.247

AC:

11057

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.445

AC:

11621

AN:

26136

East Asian (EAS)

AF:

0.286

AC:

11364

AN:

39696

South Asian (SAS)

AF:

0.383

AC:

33068

AN:

86254

European-Finnish (FIN)

AF:

0.522

AC:

27863

AN:

53418

Middle Eastern (MID)

AF:

0.441

AC:

2543

AN:

5768

European-Non Finnish (NFE)

AF:

0.496

AC:

551026

AN:

1111996

Other (OTH)

AF:

0.452

AC:

27309

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

26243

52486

78729

104972

131215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15824

31648

47472

63296

79120

<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:

0.429

AC:

65223

AN:

152162

Hom.:

14689

Cov.:

AF XY:

0.429

AC XY:

31888

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.345

AC:

14310

AN:

41508

American (AMR)

AF:

0.342

AC:

5235

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

1527

AN:

3472

East Asian (EAS)

AF:

0.269

AC:

1396

AN:

5186

South Asian (SAS)

AF:

0.383

AC:

1850

AN:

4826

European-Finnish (FIN)

AF:

0.527

AC:

5577

AN:

10588

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.497

AC:

33782

AN:

67964

Other (OTH)

AF:

0.441

AC:

933

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1914

3828

5741

7655

9569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<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:

0.473

Hom.:

71498

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

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

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 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

-0.83

CADD

Benign

1.5

(source)

DANN

Benign

0.64

PhyloP100

-3.5

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

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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