Variant 17-3589906-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000572705.2(TRPV1):c.945G>A(p.Met315Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRPV1
ENST00000572705.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.807

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042681247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRPV1	NM_080704.4 linkuse as main transcript	c.945G>A	p.Met315Ile	missense_variant	7/17	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5 linkuse as main transcript	c.945G>A	p.Met315Ile	missense_variant	6/16		NP_061197.4
TRPV1	NM_080705.4 linkuse as main transcript	c.945G>A	p.Met315Ile	missense_variant	6/16		NP_542436.2
TRPV1	NM_080706.3 linkuse as main transcript	c.945G>A	p.Met315Ile	missense_variant	5/15		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2 linkuse as main transcript	c.945G>A	p.Met315Ile	missense_variant	7/17	1	NM_080704.4	ENSP00000459962	P1	Q8NER1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000454

AC:

AN:

220190

Hom.:

AF XY:

0.00000837

AC XY:

AN XY:

119470

show subpopulations

Gnomad AFR exome

AF:

0.0000756

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1446102

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717984

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.24

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

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.79

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.027

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

M_CAP

Benign

0.0041

MetaRNN

Benign

0.043

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

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.6

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

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.62

PROVEAN

Benign

1.1

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

REVEL

Benign

0.068

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.0

B;B;B;B;B;.;B

Vest4

0.10

MutPred

0.41

Gain of catalytic residue at M315 (P = 0.0678);Gain of catalytic residue at M315 (P = 0.0678);Gain of catalytic residue at M315 (P = 0.0678);Gain of catalytic residue at M315 (P = 0.0678);Gain of catalytic residue at M315 (P = 0.0678);Gain of catalytic residue at M315 (P = 0.0678);Gain of catalytic residue at M315 (P = 0.0678);

MVP

0.23

MPC

0.070

ClinPred

0.059

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.29

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over