rs387907227
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP2PP3PP5_Moderate
The NM_020297.4(ABCC9):c.3347G>T(p.Arg1116Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1116C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_020297.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC9 | NM_020297.4 | c.3347G>T | p.Arg1116Leu | missense_variant | 29/40 | ENST00000261200.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC9 | ENST00000261200.9 | c.3347G>T | p.Arg1116Leu | missense_variant | 29/40 | 5 | NM_020297.4 | P4 | |
ENST00000539874.1 | n.331+11246C>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 01, 2016 | A variant that is likely pathogenic has been identified in the ABCC9 gene. While the R1116L variant has not been published as a pathogenic variant or reported as a benign variant, the R1116H and R1116C variants in the same residue have both been reported in patients with Cantu syndrome (Harakalova et al., 2012). The R1116H variant has been reported as a de novo variant in two additional patients with Cantu syndrome (Czeschik et al., 2013; Zhu et al., 2015). The R1116L variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R1116L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. Finally, functional studies demonstrated that the R1116H variant in the same codon results in reduced ATP sensitivity (Harakalova et al., 2012).Therefore, this variant is likely pathogenic. In order to definitively determine its clinical significance, additional data is required. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at