rs1039519

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.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

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: Ambry Genetics, Genomics England PanelApp, 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=-0.4).

BP6

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145068.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV3	NM_145068.4	MANE Select	c.270G>A	p.Gln90Gln	synonymous	Exon 4 of 18	NP_659505.1	Q8NET8-1
	TRPV3	NM_001258205.2		c.270G>A	p.Gln90Gln	synonymous	Exon 4 of 18	NP_001245134.1	Q8NET8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRPV3	ENST00000576742.6	TSL:1 MANE Select	c.270G>A	p.Gln90Gln	synonymous	Exon 4 of 18	ENSP00000461518.2	Q8NET8-1
TRPV3	ENST00000301365.8	TSL:1	c.270G>A	p.Gln90Gln	synonymous	Exon 4 of 18	ENSP00000301365.4	Q8NET8-2
TRPV3	ENST00000572519.1	TSL:1	c.270G>A	p.Gln90Gln	synonymous	Exon 4 of 17	ENSP00000460215.1	Q8NET8-3

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

GnomAD2 exomes

AF:

0.644

AC:

156912

AN:

243626

AF XY:

0.641

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 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

African (AFR)

AF:

0.553

AC:

18398

AN:

33256

American (AMR)

AF:

0.789

AC:

34886

AN:

44214

Ashkenazi Jewish (ASJ)

AF:

0.680

AC:

17720

AN:

26040

East Asian (EAS)

AF:

0.803

AC:

31592

AN:

39326

South Asian (SAS)

AF:

0.705

AC:

60385

AN:

85616

European-Finnish (FIN)

AF:

0.573

AC:

29185

AN:

50944

Middle Eastern (MID)

AF:

0.678

AC:

3893

AN:

5746

European-Non Finnish (NFE)

AF:

0.593

AC:

657785

AN:

1109804

Other (OTH)

AF:

0.626

AC:

37653

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

16175

32350

48524

64699

80874

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18164

36328

54492

72656

90820

<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:

0.603

AC:

91580

AN:

151940

Hom.:

27948

Cov.:

AF XY:

0.606

AC XY:

44962

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.562

AC:

23258

AN:

41418

American (AMR)

AF:

0.691

AC:

10545

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.682

AC:

2369

AN:

3472

East Asian (EAS)

AF:

0.788

AC:

4065

AN:

5156

South Asian (SAS)

AF:

0.702

AC:

3381

AN:

4814

European-Finnish (FIN)

AF:

0.573

AC:

6048

AN:

10552

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.588

AC:

39943

AN:

67956

Other (OTH)

AF:

0.605

AC:

1271

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1842

3685

5527

7370

9212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

768

1536

2304

3072

3840

<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:

0.600

Hom.:

53734

Bravo

AF:

0.611

Asia WGS

AF:

0.700

AC:

2436

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Isolated focal non-epidermolytic palmoplantar keratoderma (2)

Olmsted syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.2

(source)

DANN

Benign

0.73

PhyloP100

0.88

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over