rs1060499553
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PS1PM1PM2PM5PP2PP3_ModeratePP5
The NM_001127644.2(GABRA1):c.789G>A(p.Met263Ile) 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 (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin Lovd. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M263K) has been classified as Pathogenic.
Frequency
Consequence
NM_001127644.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRA1 | NM_001127644.2 | c.789G>A | p.Met263Ile | missense_variant | 8/10 | ENST00000393943.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRA1 | ENST00000393943.10 | c.789G>A | p.Met263Ile | missense_variant | 8/10 | 1 | NM_001127644.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 19 Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego | Feb 02, 2017 | The c.789G>A (p.Met263Ile) in the GABRA1 gene is a de novo missense variant. A pathogenic variant at the same amino acid position (Met263) has been reported in the literature (PMID: 26918889) This variant was not found in the 1000 Genomes, Exome Variant Server (EVS), and Exome Aggregation Consortium (ExAC) databases. Thus, it is presumed to be rare. The genomic position is highly conserved and in silico algorithms predict the variant to be damaging. Based on the combined evidence, the (p.Met263Ile) variant is classified as a likely pathogenic variant for Epileptic encephalopathy, early infantile, 19. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at