rs556886570
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_020433.5(JPH2):c.1357C>T(p.Pro453Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,544,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_020433.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
JPH2 | NM_020433.5 | c.1357C>T | p.Pro453Ser | missense_variant | 4/6 | ENST00000372980.4 | NP_065166.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
JPH2 | ENST00000372980.4 | c.1357C>T | p.Pro453Ser | missense_variant | 4/6 | 5 | NM_020433.5 | ENSP00000362071.3 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000369 AC: 5AN: 135600Hom.: 0 AF XY: 0.0000271 AC XY: 2AN XY: 73808
GnomAD4 exome AF: 0.0000129 AC: 18AN: 1391848Hom.: 0 Cov.: 34 AF XY: 0.0000131 AC XY: 9AN XY: 686572
GnomAD4 genome AF: 0.000118 AC: 18AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74462
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy 17;C5561970:Cardiomyopathy, dilated, 2E Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 20, 2021 | - - |
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 15, 2024 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 453 of the JPH2 protein (p.Pro453Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with JPH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 264361). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 28, 2022 | The p.P453S variant (also known as c.1357C>T), located in coding exon 4 of the JPH2 gene, results from a C to T substitution at nucleotide position 1357. The proline at codon 453 is replaced by serine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at