rs374748006
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001099922.3(ALG13):c.638G>A(p.Ser213Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000076 in 1,210,094 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 26 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00041 ( 0 hom., 12 hem., cov: 23)
Exomes 𝑓: 0.000042 ( 0 hom. 14 hem. )
Consequence
ALG13
NM_001099922.3 missense
NM_001099922.3 missense
Scores
3
13
Clinical Significance
Conservation
PhyloP100: 4.83
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.013918281).
BP6
Variant X-111708281-G-A is Benign according to our data. Variant chrX-111708281-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 381446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000411 (46/112019) while in subpopulation AMR AF= 0.00398 (42/10562). AF 95% confidence interval is 0.00302. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 12 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALG13 | NM_001099922.3 | c.638G>A | p.Ser213Asn | missense_variant | 4/27 | ENST00000394780.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALG13 | ENST00000394780.8 | c.638G>A | p.Ser213Asn | missense_variant | 4/27 | 2 | NM_001099922.3 | A2 | |
ALG13-AS1 | ENST00000430794.1 | n.107-1544C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.000411 AC: 46AN: 111964Hom.: 0 Cov.: 23 AF XY: 0.000352 AC XY: 12AN XY: 34138
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GnomAD3 exomes AF: 0.0000558 AC: 10AN: 179278Hom.: 0 AF XY: 0.0000597 AC XY: 4AN XY: 67000
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GnomAD4 exome AF: 0.0000419 AC: 46AN: 1098075Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 14AN XY: 363501
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GnomAD4 genome AF: 0.000411 AC: 46AN: 112019Hom.: 0 Cov.: 23 AF XY: 0.000351 AC XY: 12AN XY: 34203
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 36 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 17, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 14, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
ALG13-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 17, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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;.
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.;.
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N;.;.
REVEL
Benign
Sift
Benign
T;.;T;.;.
Sift4G
Uncertain
D;D;D;D;D
Polyphen
B;B;B;B;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at