17-3589906-C-A

Position:

• chr17-3589906-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080704.4(TRPV1):​c.945G>T​(p.Met315Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,446,102 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 6.9e-7 (0 hom.)
• Consequence: TRPV1 NM_080704.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.807

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]

ENSG00000262304 (HGNC:):

ACMG classification

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=0.044552237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV1	NM_080704.4	c.945G>T	p.Met315Ile	missense_variant	7/17	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5	c.945G>T	p.Met315Ile	missense_variant	6/16		NP_061197.4
TRPV1	NM_080705.4	c.945G>T	p.Met315Ile	missense_variant	6/16		NP_542436.2
TRPV1	NM_080706.3	c.945G>T	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	c.945G>T	p.Met315Ile	missense_variant	7/17	1	NM_080704.4	ENSP00000459962.1
ENSG00000262304	ENST00000572919.1	n.*2229G>T		non_coding_transcript_exon_variant	12/14	5		ENSP00000461416.1
ENSG00000262304	ENST00000572919.1	n.*2229G>T		3_prime_UTR_variant	12/14	5		ENSP00000461416.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1446102 Hom.: 0 Cov.: 83 AF XY: 0.00 AC XY: 0 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: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	10
DANN	Benign	0.42
DEOGEN2	Benign	0.24	T;T;T;T;.;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.79
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.027	.;.;.;T;T;T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.045	T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.6	N;N;N;N;.;.;.
PrimateAI	Uncertain	0.62	T
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		0.070	T
GERP RS		2.9
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

Other links and lift over

dbSNP: rs222747; hg19: chr17-3493200;