17-3577170-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_080704.4(TRPV1):c.1736G>A(p.Arg579His) variant causes a missense change. The variant allele was found at a frequency of 0.0000378 in 1,585,634 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 1 hom. )
Consequence
TRPV1
NM_080704.4 missense
NM_080704.4 missense
Scores
6
11
2
Clinical Significance
Conservation
PhyloP100: 4.37
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.22049475).
BS2
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRPV1 | NM_080704.4 | c.1736G>A | p.Arg579His | missense_variant | 13/17 | ENST00000572705.2 | NP_542435.2 | |
TRPV1 | NM_018727.5 | c.1736G>A | p.Arg579His | missense_variant | 12/16 | NP_061197.4 | ||
TRPV1 | NM_080705.4 | c.1736G>A | p.Arg579His | missense_variant | 12/16 | NP_542436.2 | ||
TRPV1 | NM_080706.3 | c.1736G>A | p.Arg579His | missense_variant | 11/15 | NP_542437.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRPV1 | ENST00000572705.2 | c.1736G>A | p.Arg579His | missense_variant | 13/17 | 1 | NM_080704.4 | ENSP00000459962.1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152230Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000490 AC: 10AN: 204086Hom.: 0 AF XY: 0.0000456 AC XY: 5AN XY: 109574
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GnomAD4 exome AF: 0.0000363 AC: 52AN: 1433286Hom.: 1 Cov.: 32 AF XY: 0.0000296 AC XY: 21AN XY: 710118
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GnomAD4 genome AF: 0.0000525 AC: 8AN: 152348Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74498
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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 | Mar 07, 2024 | The c.1736G>A (p.R579H) alteration is located in exon 11 (coding exon 11) of the TRPV1 gene. This alteration results from a G to A substitution at nucleotide position 1736, causing the arginine (R) at amino acid position 579 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;D;D;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;.;.;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;M;M;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;D;D;.;D
REVEL
Pathogenic
Sift
Uncertain
D;.;.;D;D;.;D
Sift4G
Uncertain
T;T;T;T;T;T;T
Polyphen
P;P;P;P;D;.;D
Vest4
MVP
MPC
0.41
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at