13-52012445-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001004127.3(ALG11):c.27C>A(p.Cys9*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,746 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 (★).
Frequency
Consequence
NM_001004127.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251044Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135814
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461746Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727146
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
ALG11-congenital disorder of glycosylation Pathogenic:1
This sequence change creates a premature translational stop signal (p.Cys9*) in the ALG11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALG11 are known to be pathogenic (PMID: 30676690). This variant is present in population databases (rs748982784, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ALG11-related conditions. ClinVar contains an entry for this variant (Variation ID: 2898658). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at