12-21807443-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP2PP3
The NM_020297.4(ABCC9):āc.4352T>Cā(p.Val1451Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,670 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 (ā ā ). Synonymous variant affecting the same amino acid position (i.e. V1451V) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC9 | NM_020297.4 | c.4352T>C | p.Val1451Ala | missense_variant | 38/40 | ENST00000261200.9 | |
LOC105369689 | XR_007063241.1 | n.632-19767A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC9 | ENST00000261200.9 | c.4352T>C | p.Val1451Ala | missense_variant | 38/40 | 5 | NM_020297.4 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251254Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135780
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461670Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727146
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 02, 2012 | The Val1451Ala variant (ABCC9) has not been reported in the literature nor previ ously identified by our laboratory. Computational analyses (biochemical amino ac id properties, conservation, AlignGVGD, and SIFT) suggest that the variant may i mpact the protein but PolyPhen-2 predicts it to be benign. However, though this information is not predictive enough to determine pathogenicity. In summary, add itional information is needed to fully assess the clinical significance of the V al1451Ala variant. - |
Dilated cardiomyopathy 1O Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | ClinVar contains an entry for this variant (Variation ID: 45414). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 27532257). This variant is present in population databases (rs397517190, gnomAD 0.006%). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1451 of the ABCC9 protein (p.Val1451Ala). 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: "Benign"; Align-GVGD: "Class C0"). 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. - |
Primary dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Blueprint Genetics | Jun 03, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at