9-128566813-C-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001130438.3(SPTAN1):c.73C>T(p.Arg25*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,866 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001130438.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461866Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727238
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
The c.73C>T (p.R25*) alteration, located in exon 2 (coding exon 1) of the SPTAN1 gene, consists of a C to T substitution at nucleotide position 73. This changes the amino acid from a arginine (R) to a stop codon at amino acid position 25. The predicted stop codon occurs in the 5' end of the SPTAN1 gene. Premature termination codons in the 5’ end of a gene have been reported to escape nonsense-mediated mRNA decay and/or lead to re-initiation (Rivas, 2015; Lindeboom, 2016; Rhee, 2017). Direct evidence for this alteration is unavailable; however, premature termination codons are typically deleterious in nature._x000D_ _x000D_ for SPTAN1-related neurologic disorders; however, its clinical significance for SPTAN1-related developmental and epileptic encephalopathy is uncertain. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as likely pathogenic. -
not provided Pathogenic:1
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge -
Developmental and epileptic encephalopathy, 5 Uncertain:1
ACMG codes: PM2 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.