17-3510841-T-G

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.*3076A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,174 control chromosomes in the GnomAD database, including 3,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3960 hom., cov: 33)
  • Exomes 𝑓: 0.21 (0 hom.)
• Consequence: TRPV3 NM_145068.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.564

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=-0.82).
• BP6: Variant 17-3510841-T-G is Benign according to our data. Variant chr17-3510841-T-G is described in ClinVar as [Benign]. Clinvar id is 322681.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV3	NM_145068.4	c.*3076A>C		3_prime_UTR_variant	18/18	ENST00000576742.6
TRPV3	NM_001258205.2	c.*3076A>C		3_prime_UTR_variant	18/18
SPATA22	NM_001321336.2	c.-74+2571A>C		intron_variant
SPATA22	NM_001321337.2	c.-74+2571A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV3	ENST00000576742.6	c.*3076A>C		3_prime_UTR_variant	18/18	1	NM_145068.4	P4

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33419 AN: 152042 Hom.: 3959 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.00983

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.216

GnomAD4 exome AF: 0.214 AC: 3 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 3 AN XY: 12

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.220 AC: 33433 AN: 152160 Hom.: 3960 Cov.: 33 AF XY: 0.212 AC XY: 15767 AN XY: 74382

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.00986

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.213

Alfa AF: 0.240 Hom.: 489

Bravo AF: 0.218

Asia WGS AF: 0.0590 AC: 207 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 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.0
Dann	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9913028; hg19: chr17-3414135;