rs1554965292
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001191061.2(SLC25A22):āc.883A>Gā(p.Ile295Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000961 in 1,456,410 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 34)
Exomes š: 0.0000096 ( 0 hom. )
Consequence
SLC25A22
NM_001191061.2 missense
NM_001191061.2 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 5.01
Genes affected
SLC25A22 (HGNC:19954): (solute carrier family 25 member 22) This gene encodes a mitochondrial glutamate carrier. Mutations in this gene are associated with early infantile epileptic encephalopathy. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC25A22 | NM_001191061.2 | c.883A>G | p.Ile295Val | missense_variant | 10/10 | ENST00000628067.3 | NP_001177990.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC25A22 | ENST00000628067.3 | c.883A>G | p.Ile295Val | missense_variant | 10/10 | 1 | NM_001191061.2 | ENSP00000486058.1 | ||
SLC25A22 | ENST00000320230.9 | c.883A>G | p.Ile295Val | missense_variant | 10/10 | 1 | ENSP00000322020.5 | |||
SLC25A22 | ENST00000531214.5 | c.883A>G | p.Ile295Val | missense_variant | 10/10 | 2 | ENSP00000437236.1 | |||
SLC25A22 | ENST00000481290.5 | c.*19A>G | downstream_gene_variant | 5 | ENSP00000431829.2 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 genomes
Cov.:
34
GnomAD3 exomes AF: 0.00000425 AC: 1AN: 235046Hom.: 0 AF XY: 0.00000777 AC XY: 1AN XY: 128768
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GnomAD4 exome AF: 0.00000961 AC: 14AN: 1456410Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 724326
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GnomAD4 genome Cov.: 34
GnomAD4 genome
Cov.:
34
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 08, 2017 | This sequence change replaces isoleucine with valine at codon 295 of the SLC25A22 protein (p.Ile295Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SLC25A22-related disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N
REVEL
Uncertain
Sift
Benign
T;.;T
Sift4G
Benign
T;T;T
Polyphen
D;D;D
Vest4
MutPred
Gain of methylation at R291 (P = 0.1117);Gain of methylation at R291 (P = 0.1117);Gain of methylation at R291 (P = 0.1117);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at