rs10793285

Positions:

• chr11-78100150-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000679559.1(ALG8):​c.1452+943C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,002 control chromosomes in the GnomAD database, including 11,724 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (11724 hom., cov: 32)
• Consequence: ALG8 ENST00000679559.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG8	ENST00000679559.1	c.1452+943C>A		intron_variant				ENSP00000505433
ALG8	ENST00000680398.1	c.1452+943C>A		intron_variant				ENSP00000506189

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56908 AN: 151884 Hom.: 11712 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.385

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.375 AC: 56940 AN: 152002 Hom.: 11724 Cov.: 32 AF XY: 0.379 AC XY: 28141 AN XY: 74294

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.392

Alfa AF: 0.437 Hom.: 15057

Bravo AF: 0.354

Asia WGS AF: 0.413 AC: 1438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10793285; hg19: chr11-77811196;