rs121908022
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_024740.2(ALG9):c.1588G>A(p.Glu530Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,650 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
ALG9
NM_024740.2 missense
NM_024740.2 missense
Scores
10
4
2
Clinical Significance
Conservation
PhyloP100: 7.84
Genes affected
ALG9 (HGNC:15672): (ALG9 alpha-1,2-mannosyltransferase) This gene encodes an alpha-1,2-mannosyltransferase enzyme that functions in lipid-linked oligosaccharide assembly. Mutations in this gene result in congenital disorder of glycosylation type Il. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.813
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALG9 | NM_024740.2 | c.1588G>A | p.Glu530Lys | missense_variant | 13/15 | ENST00000616540.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALG9 | ENST00000616540.5 | c.1588G>A | p.Glu530Lys | missense_variant | 13/15 | 1 | NM_024740.2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249366Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135282
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461650Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727136
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ALG9 congenital disorder of glycosylation Pathogenic:1Uncertain:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2004 | - - |
Uncertain significance, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 17, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;.;.;.
MutationTaster
Benign
A;A
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;.;.;D;.
Vest4
MutPred
Gain of methylation at E523 (P = 0.0153);.;.;.;.;
MVP
MPC
1.1
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -14
Find out detailed SpliceAI scores and Pangolin per-transcript scores at