rs936639741
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001191061.2(SLC25A22):c.271C>T(p.Arg91Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,314 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001191061.2 stop_gained
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 |
---|---|---|---|---|---|---|---|
SLC25A22 | NM_001191061.2 | c.271C>T | p.Arg91Ter | stop_gained | 5/10 | ENST00000628067.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A22 | ENST00000628067.3 | c.271C>T | p.Arg91Ter | stop_gained | 5/10 | 1 | NM_001191061.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461314Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 726958
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 13, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 530429). This variant has not been reported in the literature in individuals affected with SLC25A22-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg91*) in the SLC25A22 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC25A22 are known to be pathogenic (PMID: 15592994, 19780765). - |
Developmental and epileptic encephalopathy, 3 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | 3billion | Sep 01, 2022 | The variant is not observed in the gnomAD v2.1.1 dataset. This stop-gained (nonsense) variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The homozygous variant has been reported to be associated with SLC25A22-related disorder (ClinVar ID: VCV000530429/ PMID: 31589614). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at