17-3510866-T-C

Position:

• chr17-3510866-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145068.4(TRPV3):​c.*3051A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,278 control chromosomes in the GnomAD database, including 10,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (10798 hom., cov: 33)
  • Exomes 𝑓: 0.47 (2 hom.)
• Consequence: TRPV3 NM_145068.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.804

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]

SPATA22 (HGNC:30705): (spermatogenesis associated 22) Predicted to be involved in regulation of meiotic cell cycle. Predicted to act upstream of or within several processes, including fertilization; gamete generation; and meiosis I cell cycle process. Predicted to be located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-3510866-T-C is Benign according to our data. Variant chr17-3510866-T-C is described in ClinVar as [Benign]. Clinvar id is 322682.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV3	NM_145068.4	c.*3051A>G		3_prime_UTR_variant	18/18	ENST00000576742.6
TRPV3	NM_001258205.2	c.*3051A>G		3_prime_UTR_variant	18/18
SPATA22	NM_001321336.2	c.-74+2546A>G		intron_variant
SPATA22	NM_001321337.2	c.-74+2546A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV3	ENST00000576742.6	c.*3051A>G		3_prime_UTR_variant	18/18	1	NM_145068.4	P4

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52683 AN: 152130 Hom.: 10786 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.380

GnomAD4 exome AF: 0.467 AC: 14 AN: 30 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 11 AN XY: 22

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.346 AC: 52699 AN: 152248 Hom.: 10798 Cov.: 33 AF XY: 0.359 AC XY: 26702 AN XY: 74440

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.384

Alfa AF: 0.325 Hom.: 1307

Bravo AF: 0.339

Asia WGS AF: 0.625 AC: 2176 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Isolated focal non-epidermolytic palmoplantar keratoderma Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.0
DANN	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2271158; hg19: chr17-3414160;