rs763074253
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PP2PP3_Moderate
The NM_020297.4(ABCC9):c.884G>A(p.Arg295Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,682 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 (★). Synonymous variant affecting the same amino acid position (i.e. R295R) has been classified as Likely benign.
Frequency
Consequence
NM_020297.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC9 | NM_020297.4 | c.884G>A | p.Arg295Gln | missense_variant | 8/40 | ENST00000261200.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC9 | ENST00000261200.9 | c.884G>A | p.Arg295Gln | missense_variant | 8/40 | 5 | NM_020297.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151466Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250516Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135376
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461216Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726900
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151466Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 73900
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1O Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 24, 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 569093). This variant has not been reported in the literature in individuals affected with ABCC9-related conditions. This variant is present in population databases (rs763074253, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 295 of the ABCC9 protein (p.Arg295Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at