rs150255709
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_020297.4(ABCC9):c.1979G>A(p.Arg660Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,613,920 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. R660W) has been classified as Uncertain significance.
Frequency
Consequence
NM_020297.4 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 | UniProt |
---|---|---|---|---|---|---|---|
ABCC9 | NM_020297.4 | c.1979G>A | p.Arg660Gln | missense_variant | 16/40 | ENST00000261200.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC9 | ENST00000261200.9 | c.1979G>A | p.Arg660Gln | missense_variant | 16/40 | 5 | NM_020297.4 | P4 | |
ENST00000539874.1 | n.413-5042C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152064Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251352Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135832
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461738Hom.: 0 Cov.: 30 AF XY: 0.0000206 AC XY: 15AN XY: 727176
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74402
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1O Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 07, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 660 of the ABCC9 protein (p.Arg660Gln). This variant is present in population databases (rs150255709, gnomAD 0.03%). 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: 464658). 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 with a negative predictive value of 95%. 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 | Jul 08, 2021 | The p.R660Q variant (also known as c.1979G>A), located in coding exon 14 of the ABCC9 gene, results from a G to A substitution at nucleotide position 1979. The arginine at codon 660 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is 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. - |
Hypertrichotic osteochondrodysplasia Cantu type;C1837839:Dilated cardiomyopathy 1O;C3279695:Atrial fibrillation, familial, 12;C5676904:Intellectual disability and myopathy syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 23, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at