chr17-3566826-C-A

Variant names:

• chr17-3566826-C-A
• rs201622414
• NM_080704.4:c.2509G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080704.4(TRPV1):​c.2509G>T​(p.Gly837Trp) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TRPV1 NM_080704.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.779

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2778979).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4	c.2509G>T	p.Gly837Trp	missense_variant	Exon 17 of 17	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5	c.2509G>T	p.Gly837Trp	missense_variant	Exon 16 of 16		NP_061197.4
TRPV1	NM_080705.4	c.2509G>T	p.Gly837Trp	missense_variant	Exon 16 of 16		NP_542436.2
TRPV1	NM_080706.3	c.2509G>T	p.Gly837Trp	missense_variant	Exon 15 of 15		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2	c.2509G>T	p.Gly837Trp	missense_variant	Exon 17 of 17	1	NM_080704.4	ENSP00000459962.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T;T;T;T;.;.;.
Eigen	Benign	-0.063
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.51	.;.;.;T;T;T;T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.28	T;T;T;T;T;T;T
MetaSVM	Uncertain	0.037	D
MutationAssessor	Benign	1.8	L;L;L;L;.;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.0	N;.;.;N;N;.;N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0010	D;.;.;D;D;.;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D;D;D
Polyphen		0.99	D;D;D;D;D;.;D
Vest4		0.37
MutPred		0.18		.;.;.;.;Loss of relative solvent accessibility (P = 0.0186);.;.;
MVP		0.69
MPC		0.37
ClinPred		0.76	D
GERP RS		3.8
Varity_R		0.12
gMVP		0.32

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

Other links and lift over

dbSNP: rs201622414; hg19: chr17-3470120;