rs76707654
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_024105.4(ALG12):c.99G>A(p.Val33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,614,138 control chromosomes in the GnomAD database, including 738 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.042 ( 302 hom., cov: 33)
Exomes 𝑓: 0.014 ( 436 hom. )
Consequence
ALG12
NM_024105.4 synonymous
NM_024105.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.378
Genes affected
ALG12 (HGNC:19358): (ALG12 alpha-1,6-mannosyltransferase) This gene encodes a member of the glycosyltransferase 22 family. The encoded protein catalyzes the addition of the eighth mannose residue in an alpha-1,6 linkage onto the dolichol-PP-oligosaccharide precursor (dolichol-PP-Man(7)GlcNAc(2)) required for protein glycosylation. Mutations in this gene have been associated with congenital disorder of glycosylation type Ig (CDG-Ig)characterized by abnormal N-glycosylation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant 22-49913667-C-T is Benign according to our data. Variant chr22-49913667-C-T is described in ClinVar as [Benign]. Clinvar id is 342060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.378 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALG12 | NM_024105.4 | c.99G>A | p.Val33= | synonymous_variant | 2/10 | ENST00000330817.11 | |
ALG12 | XM_017028936.2 | c.99G>A | p.Val33= | synonymous_variant | 2/10 | ||
ALG12 | XM_017028937.2 | c.99G>A | p.Val33= | synonymous_variant | 2/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALG12 | ENST00000330817.11 | c.99G>A | p.Val33= | synonymous_variant | 2/10 | 1 | NM_024105.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0414 AC: 6307AN: 152200Hom.: 302 Cov.: 33
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GnomAD3 exomes AF: 0.0193 AC: 4855AN: 251366Hom.: 161 AF XY: 0.0180 AC XY: 2449AN XY: 135904
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GnomAD4 exome AF: 0.0142 AC: 20710AN: 1461820Hom.: 436 Cov.: 33 AF XY: 0.0144 AC XY: 10437AN XY: 727208
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GnomAD4 genome ? AF: 0.0415 AC: 6324AN: 152318Hom.: 302 Cov.: 33 AF XY: 0.0407 AC XY: 3031AN XY: 74484
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
ALG12-congenital disorder of glycosylation Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 06, 2020 | - - |
Computational scores
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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