chr12-21875665-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_020297.4(ABCC9):c.2081G>A(p.Arg694Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,610,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R694P) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC9 | NM_020297.4 | c.2081G>A | p.Arg694Gln | missense_variant | 17/40 | ENST00000261200.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC9 | ENST00000261200.9 | c.2081G>A | p.Arg694Gln | missense_variant | 17/40 | 5 | NM_020297.4 | P4 | |
ENST00000539874.1 | n.412+6003C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152120Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000111 AC: 28AN: 251130Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135786
GnomAD4 exome AF: 0.0000480 AC: 70AN: 1458544Hom.: 0 Cov.: 29 AF XY: 0.0000703 AC XY: 51AN XY: 725936
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74434
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 | Apr 17, 2012 | Variant classified as Uncertain Significance - Favor Benign. The Arg694Gln varia nt (ABCC9) has not been reported in the literature nor previously identified by our laboratory. Arginine (Arg) at position 694 is not conserved in mammals, and rhesus monkey has a glutamine (Gln; this variant) at this position, suggesting t he Arg694Gln variant may be tolerated. Computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Although the lack of conservation in ma mmals supports that the Arg694Gln variant may be benign, additional studies are needed to fully assess its clinical significance. - |
Dilated cardiomyopathy 1O Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at