Variant 17-3573898-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000572705.2(TRPV1):c.1838C>T(p.Ser613Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000571 in 1,610,686 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 1 hom., cov: 30)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

TRPV1
ENST00000572705.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.155

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057740092).

BS2

High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRPV1	NM_080704.4 linkuse as main transcript	c.1838C>T	p.Ser613Leu	missense_variant	14/17	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5 linkuse as main transcript	c.1838C>T	p.Ser613Leu	missense_variant	13/16		NP_061197.4
TRPV1	NM_080705.4 linkuse as main transcript	c.1838C>T	p.Ser613Leu	missense_variant	13/16		NP_542436.2
TRPV1	NM_080706.3 linkuse as main transcript	c.1838C>T	p.Ser613Leu	missense_variant	12/15		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2 linkuse as main transcript	c.1838C>T	p.Ser613Leu	missense_variant	14/17	1	NM_080704.4	ENSP00000459962	P1	Q8NER1-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

151894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000899

AC:

AN:

244748

Hom.:

AF XY:

0.0000826

AC XY:

AN XY:

133232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000119

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000521

AC:

AN:

1458674

Hom.:

Cov.:

AF XY:

0.0000565

AC XY:

AN XY:

725746

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000915

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000423

Gnomad4 OTH exome

AF:

0.0000831

GnomAD4 genome

AF:

0.000105

AC:

AN:

152012

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000677

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000827

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

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

Dec 28, 2023

The c.1838C>T (p.S613L) alteration is located in exon 12 (coding exon 12) of the TRPV1 gene. This alteration results from a C to T substitution at nucleotide position 1838, causing the serine (S) at amino acid position 613 to be replaced by a leucine (L). 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

0.068

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.28

CADD

Benign

3.0

DANN

Benign

0.94

DEOGEN2

Uncertain

0.68

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

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.72

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

M_CAP

Benign

0.048

MetaRNN

Benign

0.058

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

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.0

L;L;L;L;.;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.97

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

REVEL

Benign

0.26

Sift

Benign

0.31

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

Sift4G

Benign

0.33

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

Polyphen

0.0

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

Vest4

0.035

MVP

0.24

MPC

0.058

ClinPred

0.020

GERP RS

-6.0

Varity_R

0.031

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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