rs140158304
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_013339.4(ALG6):c.1398A>T(p.Leu466=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,613,872 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0015 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
ALG6
NM_013339.4 synonymous
NM_013339.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.253
Genes affected
ALG6 (HGNC:23157): (ALG6 alpha-1,3-glucosyltransferase) This gene encodes a member of the ALG6/ALG8 glucosyltransferase family. The encoded protein catalyzes the addition of the first glucose residue to the growing lipid-linked oligosaccharide precursor of N-linked glycosylation. Mutations in this gene are associated with congenital disorders of glycosylation type Ic. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 1-63436894-A-T is Benign according to our data. Variant chr1-63436894-A-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 382062.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2, Benign=1}.
BP7
?
Synonymous conserved (PhyloP=-0.253 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00154 (235/152234) while in subpopulation AFR AF= 0.00541 (225/41556). AF 95% confidence interval is 0.00483. There are 2 homozygotes in gnomad4. There are 123 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALG6 | NM_013339.4 | c.1398A>T | p.Leu466= | synonymous_variant | 15/15 | ENST00000263440.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALG6 | ENST00000263440.6 | c.1398A>T | p.Leu466= | synonymous_variant | 15/15 | 5 | NM_013339.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00154 AC: 234AN: 152116Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000355 AC: 89AN: 250964Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135628
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GnomAD4 exome AF: 0.000158 AC: 231AN: 1461638Hom.: 0 Cov.: 31 AF XY: 0.000143 AC XY: 104AN XY: 727126
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GnomAD4 genome ? AF: 0.00154 AC: 235AN: 152234Hom.: 2 Cov.: 32 AF XY: 0.00165 AC XY: 123AN XY: 74428
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
ALG6-congenital disorder of glycosylation 1C Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 10, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 05, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 28, 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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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