NM_001191061.2:c.235G>A
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3
The NM_001191061.2(SLC25A22):c.235G>A(p.Glu79Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001191061.2 missense
Scores
Clinical Significance
Conservation
Publications
- genetic developmental and epileptic encephalopathyInheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- developmental and epileptic encephalopathy, 3Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- early myoclonic encephalopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- malignant migrating partial seizures of infancyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD2 exomes AF: 0.00000401 AC: 1AN: 249390 AF XY: 0.00000740 show subpopulations
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459454Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726040 show subpopulations
Age Distribution
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy Uncertain:1
This sequence change replaces glutamic acid with lysine at codon 79 of the SLC25A22 protein (p.Glu79Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with developmental delay, seizures and hypotonia (PMID: 28255779). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at