chr12-21815804-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_020297.4(ABCC9):c.3982G>A(p.Val1328Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,208 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. V1328V) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC9 | NM_020297.4 | c.3982G>A | p.Val1328Ile | missense_variant | 34/40 | ENST00000261200.9 | |
LOC105369689 | XR_007063241.1 | n.632-11406C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC9 | ENST00000261200.9 | c.3982G>A | p.Val1328Ile | missense_variant | 34/40 | 5 | NM_020297.4 | P4 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461208Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726942
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1O Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2016 | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an ABCC9-related disease. This sequence change replaces valine with isoleucine at codon 1328 of the ABCC9 protein (p.Val1328Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at