rs199473705

Variant names:

• chr17-3518587-A-C
• rs199473705
• NM_145068.4:c.2074T>G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_145068.4(TRPV3):​c.2074T>G​(p.Trp692Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRPV3 NM_145068.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:2 O:1
• Conservation: PhyloP100: 8.90

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.982
• PP5: Variant 17-3518587-A-C is Pathogenic according to our data. Variant chr17-3518587-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 30638.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-3518587-A-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV3	NM_145068.4	c.2074T>G	p.Trp692Gly	missense_variant	Exon 15 of 18	ENST00000576742.6	NP_659505.1
TRPV3	NM_001258205.2	c.2074T>G	p.Trp692Gly	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.2074T>G	p.Trp692Gly	missense_variant	Exon 15 of 18	1	NM_145068.4	ENSP00000461518.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00209 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Pathogenic:1 Other:1

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Lab of Dermatology, Peking University First Hospital

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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UniProtKB/Swiss-Prot

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Olmsted syndrome 1 Pathogenic:1

Mar 09, 2012

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.60	.;.;D;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Pathogenic	0.57	D
MetaRNN	Pathogenic	0.98	D;D;D;D
MetaSVM	Pathogenic	0.94	D
MutationAssessor	Pathogenic	2.9	.;M;M;M
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-12	.;D;.;.
REVEL	Pathogenic	0.94
Sift	Pathogenic	0.0	.;D;.;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0, 1.0	.;D;D;D
Vest4		0.99
MutPred		0.80		.;Gain of disorder (P = 0.0021);Gain of disorder (P = 0.0021);Gain of disorder (P = 0.0021);
MVP		0.86
MPC		0.94
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.93
gMVP		0.95

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

LitVar

Other links and lift over

dbSNP: rs199473705; hg19: chr17-3421881;