17-3518181-A-G

Position:

• chr17-3518181-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
TRPV3	NM_145068.4	c.2085+395T>C		intron_variant		ENST00000576742.6	NP_659505.1
TRPV3	NM_001258205.2	c.2085+395T>C		intron_variant			NP_001245134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV3	ENST00000576742.6	c.2085+395T>C		intron_variant		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

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.951

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.644

Alfa AF: 0.545 Hom.: 38303

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

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