rs760819207
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001099922.3(ALG13):c.3241G>A(p.Gly1081Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000273 in 1,097,614 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )
Consequence
ALG13
NM_001099922.3 missense
NM_001099922.3 missense
Scores
4
13
Clinical Significance
Conservation
PhyloP100: 4.31
Genes affected
ALG13 (HGNC:30881): (ALG13 UDP-N-acetylglucosaminyltransferase subunit) The protein encoded by this gene is a subunit of a bipartite UDP-N-acetylglucosamine transferase. It heterodimerizes with asparagine-linked glycosylation 14 homolog to form a functional UDP-GlcNAc glycosyltransferase that catalyzes the second sugar addition of the highly conserved oligosaccharide precursor in endoplasmic reticulum N-linked glycosylation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.23125625).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALG13 | NM_001099922.3 | c.3241G>A | p.Gly1081Ser | missense_variant | 27/27 | ENST00000394780.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALG13 | ENST00000394780.8 | c.3241G>A | p.Gly1081Ser | missense_variant | 27/27 | 2 | NM_001099922.3 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD3 exomes AF: 0.00000563 AC: 1AN: 177764Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 65764
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GnomAD4 exome AF: 0.00000273 AC: 3AN: 1097614Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1AN XY: 363182
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GnomAD4 genome ? Cov.: 22
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22
ExAC
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 36 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2021 | This sequence change replaces glycine with serine at codon 1081 of the ALG13 protein (p.Gly1081Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs760819207, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with ALG13-related conditions. ClinVar contains an entry for this variant (Variation ID: 579505). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;.;T;.
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.;.
MutationTaster
Benign
D;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N;.;.
REVEL
Benign
Sift
Uncertain
D;.;D;.;.
Sift4G
Benign
T;T;T;T;T
Polyphen
P;D;D;D;D
Vest4
MutPred
Loss of relative solvent accessibility (P = 0.0071);.;.;.;.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at