11-78100944-T-C

Position:

• chr11-78100944-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000525783(ALG8):​c.*20A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 1,599,156 control chromosomes in the GnomAD database, including 566,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (56459 hom., cov: 33)
  • Exomes 𝑓: 0.84 (510046 hom.)
• Consequence: ALG8 ENST00000525783 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.433

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-78100944-T-C is Benign according to our data. Variant chr11-78100944-T-C is described in ClinVar as [Benign]. Clinvar id is 96088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-78100944-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG8	NM_024079.5	c.*20A>G		downstream_gene_variant		ENST00000299626.10	NP_076984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG8	ENST00000299626.10	c.*20A>G		downstream_gene_variant		1	NM_024079.5	ENSP00000299626.5

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130567 AN: 152160 Hom.: 56404 Cov.: 33

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.858

GnomAD3 exomes AF: 0.823 AC: 206457 AN: 250820 Hom.: 85616 AF XY: 0.828 AC XY: 112170 AN XY: 135550

Gnomad AFR exome AF: 0.937

Gnomad AMR exome AF: 0.691

Gnomad ASJ exome AF: 0.868

Gnomad EAS exome AF: 0.758

Gnomad SAS exome AF: 0.833

Gnomad FIN exome AF: 0.836

Gnomad NFE exome AF: 0.848

Gnomad OTH exome AF: 0.839

GnomAD4 exome AF: 0.838 AC: 1212893 AN: 1446878 Hom.: 510046 Cov.: 28 AF XY: 0.838 AC XY: 604312 AN XY: 720880

Gnomad4 AFR exome AF: 0.941

Gnomad4 AMR exome AF: 0.703

Gnomad4 ASJ exome AF: 0.870

Gnomad4 EAS exome AF: 0.695

Gnomad4 SAS exome AF: 0.828

Gnomad4 FIN exome AF: 0.837

Gnomad4 NFE exome AF: 0.845

Gnomad4 OTH exome AF: 0.847

GnomAD4 genome AF: 0.858 AC: 130681 AN: 152278 Hom.: 56459 Cov.: 33 AF XY: 0.854 AC XY: 63584 AN XY: 74452

Gnomad4 AFR AF: 0.936

Gnomad4 AMR AF: 0.759

Gnomad4 ASJ AF: 0.872

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.837

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.860

Alfa AF: 0.844 Hom.: 42179

Bravo AF: 0.856

Asia WGS AF: 0.802 AC: 2792 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 25, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

ALG8 congenital disorder of glycosylation Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Congenital disorder of glycosylation Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1263505; hg19: chr11-77811990;