X-111681231-T-C
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_001099922.3(ALG13):c.13T>C(p.Phe5Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000121 in 1,210,771 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 43 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., 2 hem., cov: 25)
Exomes 𝑓: 0.00012 ( 0 hom. 41 hem. )
Consequence
ALG13
NM_001099922.3 missense
NM_001099922.3 missense
Scores
6
6
4
Clinical Significance
Conservation
PhyloP100: 5.03
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 -16 ACMG points.
BP6
?
Variant X-111681231-T-C is Benign according to our data. Variant chrX-111681231-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 516978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000133 (15/112746) while in subpopulation NFE AF= 0.000263 (14/53233). AF 95% confidence interval is 0.000158. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALG13 | NM_001099922.3 | c.13T>C | p.Phe5Leu | missense_variant | 1/27 | ENST00000394780.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALG13 | ENST00000394780.8 | c.13T>C | p.Phe5Leu | missense_variant | 1/27 | 2 | NM_001099922.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000133 AC: 15AN: 112746Hom.: 0 Cov.: 25 AF XY: 0.0000573 AC XY: 2AN XY: 34910
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GnomAD3 exomes AF: 0.0000928 AC: 17AN: 183172Hom.: 0 AF XY: 0.0000591 AC XY: 4AN XY: 67632
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GnomAD4 exome AF: 0.000120 AC: 132AN: 1098025Hom.: 0 Cov.: 30 AF XY: 0.000113 AC XY: 41AN XY: 363383
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 04, 2018 | 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 | May 09, 2023 | 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. - |
Developmental and epileptic encephalopathy, 36 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;D;T;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;.;.
MutationTaster
Benign
D;N;N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;N;.;.
REVEL
Uncertain
Sift
Pathogenic
D;D;.;.
Sift4G
Pathogenic
D;D;D;D
Polyphen
B;D;.;.
Vest4
MutPred
Loss of catalytic residue at F5 (P = 0.0137);Loss of catalytic residue at F5 (P = 0.0137);Loss of catalytic residue at F5 (P = 0.0137);Loss of catalytic residue at F5 (P = 0.0137);
MVP
MPC
0.23
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at