17-3566969-T-C

Position:

• chr17-3566969-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080704.4(TRPV1):​c.2366A>G​(p.Lys789Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TRPV1 NM_080704.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.39

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19199425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV1	NM_080704.4	c.2366A>G	p.Lys789Arg	missense_variant	17/17	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5	c.2366A>G	p.Lys789Arg	missense_variant	16/16		NP_061197.4
TRPV1	NM_080705.4	c.2366A>G	p.Lys789Arg	missense_variant	16/16		NP_542436.2
TRPV1	NM_080706.3	c.2366A>G	p.Lys789Arg	missense_variant	15/15		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2	c.2366A>G	p.Lys789Arg	missense_variant	17/17	1	NM_080704.4	ENSP00000459962.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 17, 2024

The c.2366A>G (p.K789R) alteration is located in exon 15 (coding exon 15) of the TRPV1 gene. This alteration results from a A to G substitution at nucleotide position 2366, causing the lysine (K) at amino acid position 789 to be replaced by an arginine (R). 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	0.079
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T;T;T;.;.;.
Eigen	Benign	-0.11
Eigen_PC	Benign	0.023
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.74	.;.;.;T;T;T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.19	T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.028	T
MutationAssessor	Uncertain	2.2	M;M;M;M;.;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.48	N;.;.;N;N;.;N
REVEL	Uncertain	0.48
Sift	Benign	0.15	T;.;.;T;T;.;T
Sift4G	Benign	0.20	T;T;T;T;T;T;T
Polyphen		0.027	B;B;B;B;B;.;P
Vest4		0.16
MutPred		0.26		.;.;.;.;Gain of loop (P = 0.0166);.;.;
MVP		0.59
MPC		0.057
ClinPred		0.55	D
GERP RS		4.3
Varity_R		0.065
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-3470263;