rs1039519

Positions:

• chr17-3544620-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.882

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 -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 id is 322795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-3544620-C-T is described in Lovd as [Benign].
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV3	NM_145068.4	c.270G>A	p.Gln90Gln	synonymous_variant	4/18	ENST00000576742.6	NP_659505.1
TRPV3	NM_001258205.2	c.270G>A	p.Gln90Gln	synonymous_variant	4/18		NP_001245134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV3	ENST00000576742.6	c.270G>A	p.Gln90Gln	synonymous_variant	4/18	1	NM_145068.4	ENSP00000461518.2

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91504 AN: 151822 Hom.: 27926 Cov.: 31

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

GnomAD3 exomes AF: 0.644 AC: 156912 AN: 243626 Hom.: 51828 AF XY: 0.641 AC XY: 84590 AN XY: 131906

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 SAS exome AF: 0.702

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.: 45 AF XY: 0.615 AC XY: 444860 AN XY: 723756

Gnomad4 AFR exome AF: 0.553

Gnomad4 AMR exome AF: 0.789

Gnomad4 ASJ exome AF: 0.680

Gnomad4 EAS exome AF: 0.803

Gnomad4 SAS exome AF: 0.705

Gnomad4 FIN exome AF: 0.573

Gnomad4 NFE exome AF: 0.593

Gnomad4 OTH exome AF: 0.626

GnomAD4 genome AF: 0.603 AC: 91580 AN: 151940 Hom.: 27948 Cov.: 31 AF XY: 0.606 AC XY: 44962 AN XY: 74236

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.605

Alfa AF: 0.598 Hom.: 39215

Bravo AF: 0.611

Asia WGS AF: 0.700 AC: 2436 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Isolated focal non-epidermolytic palmoplantar keratoderma Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Olmsted syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	9.2
DANN	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs1039519; hg19: chr17-3447914; COSMIC: COSV56791895;