Variant 17-3566832-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000572705.2(TRPV1):c.2503G>A(p.Ala835Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TRPV1
ENST00000572705.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.305

Variant links:

Genes affected

TRPV1 (HGNC:12716): (transient receptor potential cation channel subfamily V member 1) Capsaicin, the main pungent ingredient in hot chili peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system. The protein encoded by this gene is a receptor for capsaicin and is a non-selective cation channel that is structurally related to members of the TRP family of ion channels. This receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo. Four transcript variants encoding the same protein, but with different 5' UTR sequence, have been described for this gene. [provided by RefSeq, Jul 2008]

TRPV1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13715264).

BS2

High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRPV1	NM_080704.4 linkuse as main transcript	c.2503G>A	p.Ala835Thr	missense_variant	17/17	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5 linkuse as main transcript	c.2503G>A	p.Ala835Thr	missense_variant	16/16		NP_061197.4
TRPV1	NM_080705.4 linkuse as main transcript	c.2503G>A	p.Ala835Thr	missense_variant	16/16		NP_542436.2
TRPV1	NM_080706.3 linkuse as main transcript	c.2503G>A	p.Ala835Thr	missense_variant	15/15		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2 linkuse as main transcript	c.2503G>A	p.Ala835Thr	missense_variant	17/17	1	NM_080704.4	ENSP00000459962	P1	Q8NER1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000442

AC:

AN:

249092

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000223

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461560

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000414

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2022

The c.2503G>A (p.A835T) alteration is located in exon 15 (coding exon 15) of the TRPV1 gene. This alteration results from a G to A substitution at nucleotide position 2503, causing the alanine (A) at amino acid position 835 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.19

CADD

Benign

7.8

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

T;T;T;T;.;.;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.61

.;.;.;T;T;T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.14

T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

1.9

M;M;M;M;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.81

N;.;.;N;N;.;N

REVEL

Uncertain

0.32

Sift

Uncertain

0.0080

D;.;.;D;D;.;D

Sift4G

Uncertain

0.016

D;D;D;D;D;D;D

Polyphen

0.57

P;P;P;P;B;.;P

Vest4

0.045

MutPred

0.086

.;.;.;.;Gain of phosphorylation at A846 (P = 0.0244);.;.;

MVP

0.69

MPC

0.062

ClinPred

0.098

GERP RS

4.8

Varity_R

0.068

gMVP

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over