rs779720018
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM1PP2BP4
The NM_020297.4(ABCC9):c.970C>T(p.Arg324Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R324H) has been classified as Uncertain significance.
Frequency
Consequence
NM_020297.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC9 | NM_020297.4 | c.970C>T | p.Arg324Cys | missense_variant | 8/40 | ENST00000261200.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC9 | ENST00000261200.9 | c.970C>T | p.Arg324Cys | missense_variant | 8/40 | 5 | NM_020297.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151916Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250932Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135628
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461390Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727002
GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 151916Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74162
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1O Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 324 of the ABCC9 protein (p.Arg324Cys). This variant is present in population databases (rs779720018, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ABCC9-related conditions. ClinVar contains an entry for this variant (Variation ID: 282363). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ABCC9 protein function. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 28, 2015 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 01, 2023 | The p.R324C variant (also known as c.970C>T), located in coding exon 6 of the ABCC9 gene, results from a C to T substitution at nucleotide position 970. The arginine at codon 324 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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