rs1555452127
Positions:
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
Genomes: not found (cov: 33)
Consequence
ALG1
NM_019109.5 missense
NM_019109.5 missense
Scores
10
7
2
Clinical Significance
Conservation
PhyloP100: 5.30
Genes affected
ALG1 (HGNC:18294): (ALG1 chitobiosyldiphosphodolichol beta-mannosyltransferase) The enzyme encoded by this gene catalyzes the first mannosylation step in the biosynthesis of lipid-linked oligosaccharides. This gene is mutated in congenital disorder of glycosylation type Ik. [provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.878
PP5
Variant 16-5079078-T-C is Pathogenic according to our data. Variant chr16-5079078-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 522808.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALG1 | NM_019109.5 | c.877T>C | p.Ser293Pro | missense_variant | 8/13 | ENST00000262374.10 | NP_061982.3 | |
ALG1 | NM_001330504.2 | c.544T>C | p.Ser182Pro | missense_variant | 8/13 | NP_001317433.1 | ||
ALG1 | XM_017023457.3 | c.862+200T>C | intron_variant | XP_016878946.1 | ||||
ALG1 | XR_007064892.1 | n.884T>C | non_coding_transcript_exon_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALG1 | ENST00000262374.10 | c.877T>C | p.Ser293Pro | missense_variant | 8/13 | 1 | NM_019109.5 | ENSP00000262374.5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
35
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ALG1-congenital disorder of glycosylation Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Undiagnosed Diseases Network, NIH | Jun 23, 2017 | 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;T;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
.;H;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;D;D
REVEL
Pathogenic
Sift
Uncertain
.;D;D
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;D;.
Vest4
MutPred
0.60
.;Loss of phosphorylation at S293 (P = 0.0601);.;
MVP
MPC
0.16
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at