rs142875103
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS1
The NM_005691.4(ABCC9):c.4591C>T(p.Pro1531Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,613,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005691.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 151894Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251260Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135788
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461770Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727186
GnomAD4 genome AF: 0.000151 AC: 23AN: 151894Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74154
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 | Sep 22, 2015 | Variant classified as Uncertain Significance - Favor Benign. The p.Pro1531Ser va riant in ABCC9 has not been previously reported in individuals with cardiomyopat hy, but has been identified in 6/10386 of African chromosomes by the Exome Aggre gation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs142875103). Pro line (Pro) at position 1531 is not conserved in mammals or evolutionarily distan t species and >15 birds and reptiles carry a serine (Ser) at this position, rais ing the possibility that this change may be tolerated. In summary, while the cli nical significance of the p.Pro1531Ser variant is uncertain, these data suggest that it is more likely to be benign. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 21, 2023 | Identified in a patient with DCM in published literature (PMID: 31983221); In silico analysis supports that this missense variant does not alter protein structure/function; Reported using an alternate transcript of the gene; This variant is associated with the following publications: (PMID: 31983221) - |
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 | Oct 29, 2021 | - - |
Dilated cardiomyopathy 1O Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 14, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 23, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at