chr11-17395914-C-A
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PM1PM2PM5PP3_StrongPP5_Very_Strong
The NM_000352.6(ABCC8):c.4136G>T(p.Arg1379Leu) 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. R1379C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000352.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC8 | NM_000352.6 | c.4136G>T | p.Arg1379Leu | missense_variant | 34/39 | ENST00000389817.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC8 | ENST00000389817.8 | c.4136G>T | p.Arg1379Leu | missense_variant | 34/39 | 1 | NM_000352.6 | P4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1433156Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 709694
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Neonatal diabetes mellitus Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing;curation | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 18, 2011 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 16, 2019 | DNA sequence analysis of the ABCC8 gene demonstrated a sequence change, c.4136G>T, in exon 34 that results in an amino acid change, p.Arg1379Leu. The p.Arg1379Leu change has been identified in patients with transient neonatal diabetes and family members of these individuals who were diagnosed with diabetes in adulthood (PMID: 18025464). Additionally, several other mutations affecting the same amino acid residue (p.Arg1379Cys, p.Arg1379His, p.Arg1379Pro, p.Arg1379Ser) have been reported in patients with neonatal diabetes as well as adult onset diabetes (PMIDs: 18025464, 16885549, 24622368, 25555642). The p.Arg1379Leu change is absent from large population databases such as ExAC and gnomAD. The p.Arg1379Leu change affects a highly conserved amino acid residue located in a domain of the SUR1 protein that is known to be functional. The p.Arg1379Leu substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at