17-3518181-A-G

Variant names:

• chr17-3518181-A-G
• rs7217270
• NM_145068.4:c.2085+395T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145068.4(TRPV3):​c.2085+395T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 151,864 control chromosomes in the GnomAD database, including 26,930 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (26930 hom., cov: 31)
• Consequence: TRPV3 NM_145068.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.561
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• 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	c.2085+395T>C		intron_variant	Intron 15 of 17	ENST00000576742.6	NP_659505.1
TRPV3	NM_001258205.2	c.2085+395T>C		intron_variant	Intron 15 of 17		NP_001245134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV3	ENST00000576742.6	c.2085+395T>C		intron_variant	Intron 15 of 17	1	NM_145068.4	ENSP00000461518.2

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88931 AN: 151744 Hom.: 26896 Cov.: 31

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.639

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.586 AC: 89020 AN: 151864 Hom.: 26930 Cov.: 31 AF XY: 0.588 AC XY: 43658 AN XY: 74216

African (AFR) AF: 0.658 AC: 27238 AN: 41396

American (AMR) AF: 0.621 AC: 9466 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2084 AN: 3472

East Asian (EAS) AF: 0.951 AC: 4919 AN: 5170

South Asian (SAS) AF: 0.722 AC: 3474 AN: 4812

European-Finnish (FIN) AF: 0.451 AC: 4762 AN: 10550

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34982 AN: 67920

Other (OTH) AF: 0.644 AC: 1357 AN: 2108

Alfa AF: 0.548 Hom.: 89710

Bravo AF: 0.604

Asia WGS AF: 0.824 AC: 2867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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: rs7217270; hg19: chr17-3421475; COSMIC: COSV56795237; COSMIC: COSV56795237;