rs1555452127
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate
The NM_019109.5(ALG1):c.877T>C(p.Ser293Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_019109.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALG1 | NM_019109.5 | c.877T>C | p.Ser293Pro | missense_variant | Exon 8 of 13 | ENST00000262374.10 | NP_061982.3 | |
ALG1 | NM_001330504.2 | c.544T>C | p.Ser182Pro | missense_variant | Exon 8 of 13 | NP_001317433.1 | ||
ALG1 | XM_017023457.3 | c.862+200T>C | intron_variant | Intron 7 of 11 | XP_016878946.1 | |||
ALG1 | XR_007064892.1 | n.884T>C | non_coding_transcript_exon_variant | Exon 8 of 10 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 35
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
ALG1-congenital disorder of glycosylation Pathogenic:1
Clinical genome sequencing revealed 3 variants of uncertain significance in the ALG1 gene. Multiple lines of computational evidence support a deleterious effect of these variants on the gene or gene product. cDNA experiments performed on a research basis demonstrated that the paternally inherited variant (c.1187+3A>G) is damaging. The maternally inherited variants are rare and are not present in the 1000 Genomes Project nor the Exome Aggregate Consortium (ExAC) databases. Based on these findings, the clinical team elevated these variants to likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at