chr17-3573898-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_080704.4(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
NM_080704.4 missense
NM_080704.4 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: -0.155
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 Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.057740092).
BS2
?
High AC in GnomAd at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPV1 | NM_080704.4 | c.1838C>T | p.Ser613Leu | missense_variant | 14/17 | ENST00000572705.2 | |
TRPV1 | NM_018727.5 | c.1838C>T | p.Ser613Leu | missense_variant | 13/16 | ||
TRPV1 | NM_080705.4 | c.1838C>T | p.Ser613Leu | missense_variant | 13/16 | ||
TRPV1 | NM_080706.3 | c.1838C>T | p.Ser613Leu | missense_variant | 12/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPV1 | ENST00000572705.2 | c.1838C>T | p.Ser613Leu | missense_variant | 14/17 | 1 | NM_080704.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 151894Hom.: 1 Cov.: 30
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000899 AC: 22AN: 244748Hom.: 0 AF XY: 0.0000826 AC XY: 11AN XY: 133232
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GnomAD4 exome AF: 0.0000521 AC: 76AN: 1458674Hom.: 0 Cov.: 33 AF XY: 0.0000565 AC XY: 41AN XY: 725746
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152012Hom.: 1 Cov.: 30 AF XY: 0.0000808 AC XY: 6AN XY: 74292
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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 | 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Uncertain
D;D;D;D;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;.;.;.
MutationTaster
Benign
N;N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.;N;N;.;N
REVEL
Benign
Sift
Benign
T;.;.;T;T;.;T
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
B;B;B;B;B;.;B
Vest4
MVP
MPC
0.058
ClinPred
T
GERP RS
Varity_R
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