rs772296795
Variant summary
Our verdict is Pathogenic. Variant got 20 ACMG points: 20P and 0B. PVS1PM2PP3_ModeratePP5_Very_Strong
The NM_032861.4(SERAC1):c.1167_1170delTCAG(p.Gln390ProfsTer29) variant causes a frameshift, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000087 in 1,608,906 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_032861.4 frameshift, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000415 AC: 1AN: 240762Hom.: 0 AF XY: 0.00000769 AC XY: 1AN XY: 130064
GnomAD4 exome AF: 0.00000892 AC: 13AN: 1456720Hom.: 0 AF XY: 0.00000828 AC XY: 6AN XY: 724232
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74350
ClinVar
Submissions by phenotype
3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome Pathogenic:3
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The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Frameshift 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 variant has been reported to be associated with SERAC1-related disorder (ClinVar ID: VCV000035558 / PMID: 22683713). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at