rs1554965669
Variant summary
Our verdict is Pathogenic. Variant got 19 ACMG points: 19P and 0B. PVS1PM2PP3PP5_Very_Strong
The NM_001191061.2(SLC25A22):c.394C>T(p.Gln132Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000205 in 1,460,496 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 Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
SLC25A22
NM_001191061.2 stop_gained
NM_001191061.2 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 6.72
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 Pathogenic. Variant got 19 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 11-792888-G-A is Pathogenic according to our data. Variant chr11-792888-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 436749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC25A22 | NM_001191061.2 | c.394C>T | p.Gln132Ter | stop_gained | 6/10 | ENST00000628067.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A22 | ENST00000628067.3 | c.394C>T | p.Gln132Ter | stop_gained | 6/10 | 1 | NM_001191061.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460496Hom.: 0 Cov.: 40 AF XY: 0.00000413 AC XY: 3AN XY: 726566
GnomAD4 exome
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3
AN:
1460496
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40
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AC XY:
3
AN XY:
726566
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 03, 2017 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SLC25A22 are known to be pathogenic (PMID: 15592994, 19780765). This variant has been reported in the literature in an individual affected with Ohtahara syndrome (PMID: 27864847). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln132*) in the SLC25A22 gene. It is expected to result in an absent or disrupted protein product. - |
Early myoclonic encephalopathy Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 10, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at