chr17-3572188-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_080704.4(TRPV1):c.2165G>A(p.Arg722His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_080704.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRPV1 | NM_080704.4 | c.2165G>A | p.Arg722His | missense_variant | Exon 15 of 17 | ENST00000572705.2 | NP_542435.2 | |
TRPV1 | NM_018727.5 | c.2165G>A | p.Arg722His | missense_variant | Exon 14 of 16 | NP_061197.4 | ||
TRPV1 | NM_080705.4 | c.2165G>A | p.Arg722His | missense_variant | Exon 14 of 16 | NP_542436.2 | ||
TRPV1 | NM_080706.3 | c.2165G>A | p.Arg722His | missense_variant | Exon 13 of 15 | NP_542437.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152168Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000323 AC: 8AN: 247500Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 134226
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1460870Hom.: 0 Cov.: 66 AF XY: 0.0000206 AC XY: 15AN XY: 726612
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74340
ClinVar
Submissions by phenotype
Malignant hyperthermia of anesthesia Uncertain:1
This sequence change is predicted to replace arginine with histidine at codon 722 of the TRPV1 protein (p.(Arg722His)). The arginine residue is highly conserved (100 vertebrates, UCSC), and is located in the ion transport domain. There is a small physicochemical difference between arginine and histidine. The variant is present in a large population cohort at a frequency of 0.003% (rs771123129, 9/278,882 alleles, 0 homozygotes in gnomAD v2.1), with a frequency of 0.009% in the Latino/admixed American population (3/35,164 alleles in gnomAD v2.1). The variant has not been reported in the relevant medical literature or databases. Multiple lines of computational evidence predict a deleterious effect for the missense substitution (4/4 algorithms). Based on the classification scheme RMH Modified ACMG Guidelines v1.3.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PP3. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at