chr17-3518738-G-T

Variant names:

• chr17-3518738-G-T
• rs7216486
• NM_145068.4:c.1923C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145068.4(TRPV3):​c.1923C>A​(p.Asp641Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D641D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRPV3 NM_145068.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 20 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV3	NM_145068.4	c.1923C>A	p.Asp641Glu	missense_variant	Exon 15 of 18	ENST00000576742.6	NP_659505.1
TRPV3	NM_001258205.2	c.1923C>A	p.Asp641Glu	missense_variant	Exon 15 of 18		NP_001245134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV3	ENST00000576742.6	c.1923C>A	p.Asp641Glu	missense_variant	Exon 15 of 18	1	NM_145068.4	ENSP00000461518.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.70	.;.;D;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.67	T;T;T;T
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.56	D;D;D;D
MetaSVM	Uncertain	0.53	D
MutationAssessor	Benign	1.3	.;L;L;L
PhyloP100		1.7
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.5	.;D;.;.
REVEL	Uncertain	0.56
Sift	Benign	0.21	.;T;.;.
Sift4G	Benign	0.29	T;T;T;T
Polyphen		0.18, 0.78, 0.73	.;B;P;P
Vest4		0.30
MutPred		0.66		.;Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP		0.87
MPC		0.31
ClinPred		0.93	D
GERP RS		5.7
Varity_R		0.46
gMVP		0.94

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

Other links and lift over

dbSNP: rs7216486; hg19: chr17-3422032;