rs368528528
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The ENST00000297770.10(CPA6):c.1087G>A(p.Gly363Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000558 in 1,613,220 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G363A) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000297770.10 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CPA6 | NM_020361.5 | c.1087G>A | p.Gly363Arg | missense_variant | 10/11 | ENST00000297770.10 | NP_065094.3 | |
ARFGEF1-DT | NR_136224.1 | n.470-14124C>T | intron_variant, non_coding_transcript_variant | |||||
CPA6 | XM_017013646.2 | c.643G>A | p.Gly215Arg | missense_variant | 10/11 | XP_016869135.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CPA6 | ENST00000297770.10 | c.1087G>A | p.Gly363Arg | missense_variant | 10/11 | 1 | NM_020361.5 | ENSP00000297770 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152090Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251198Hom.: 1 AF XY: 0.0000737 AC XY: 10AN XY: 135772
GnomAD4 exome AF: 0.0000465 AC: 68AN: 1461130Hom.: 1 Cov.: 28 AF XY: 0.0000523 AC XY: 38AN XY: 726922
GnomAD4 genome AF: 0.000145 AC: 22AN: 152090Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74296
ClinVar
Submissions by phenotype
Febrile seizures, familial, 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 01, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 472759). This variant has not been reported in the literature in individuals affected with CPA6-related conditions. This variant is present in population databases (rs368528528, gnomAD 0.02%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 363 of the CPA6 protein (p.Gly363Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at