ENST00000679559.1:c.1452+943C>A

Variant names:

• chr11-78100150-G-T
• rs10793285
• ENST00000679559.1:c.1452+943C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

ALG8 Gene-Disease associations (from GenCC):

• ALG8-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• polycystic liver disease 3 with or without kidney cysts

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000679559.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG8	ENST00000679559.1		c.1452+943C>A		intron	N/A	ENSP00000505433.1
	ALG8	ENST00000680398.1		c.1452+943C>A		intron	N/A	ENSP00000506189.1

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

African (AFR) AF: 0.196 AC: 8108 AN: 41472

American (AMR) AF: 0.366 AC: 5582 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1418 AN: 3468

East Asian (EAS) AF: 0.362 AC: 1872 AN: 5172

South Asian (SAS) AF: 0.416 AC: 2003 AN: 4812

European-Finnish (FIN) AF: 0.548 AC: 5789 AN: 10568

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30909 AN: 67938

Other (OTH) AF: 0.392 AC: 824 AN: 2100

Alfa AF: 0.407 Hom.: 20637

Bravo AF: 0.354

Asia WGS AF: 0.413 AC: 1438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.74
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs10793285; hg19: chr11-77811196;