rs199911532
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_024079.5(ALG8):c.96-6G>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,611,630 control chromosomes in the GnomAD database, including 9 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 0.0012 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 8 hom. )
Consequence
ALG8
NM_024079.5 splice_region, splice_polypyrimidine_tract, intron
NM_024079.5 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00005400
1
Clinical Significance
Conservation
PhyloP100: -0.0160
Genes affected
ALG8 (HGNC:23161): (ALG8 alpha-1,3-glucosyltransferase) This gene encodes a member of the ALG6/ALG8 glucosyltransferase family. The encoded protein catalyzes the addition of the second glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation of proteins. Mutations in this gene have been associated with congenital disorder of glycosylation type Ih (CDG-Ih). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP6
?
Variant 11-78127442-C-G is Benign according to our data. Variant chr11-78127442-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 218479.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}. Variant chr11-78127442-C-G is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0011 (1602/1459450) while in subpopulation MID AF= 0.0142 (82/5758). AF 95% confidence interval is 0.0118. There are 8 homozygotes in gnomad4_exome. There are 815 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALG8 | NM_024079.5 | c.96-6G>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000299626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALG8 | ENST00000299626.10 | c.96-6G>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_024079.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00119 AC: 181AN: 152064Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00160 AC: 402AN: 250928Hom.: 2 AF XY: 0.00163 AC XY: 221AN XY: 135680
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GnomAD4 exome AF: 0.00110 AC: 1602AN: 1459450Hom.: 8 Cov.: 31 AF XY: 0.00112 AC XY: 815AN XY: 726228
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GnomAD4 genome ? AF: 0.00118 AC: 180AN: 152180Hom.: 1 Cov.: 32 AF XY: 0.00113 AC XY: 84AN XY: 74388
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
ALG8 congenital disorder of glycosylation Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | May 11, 2015 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | ALG8: PP3, BS2 - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at