rs10793289

chr11-78139471-C-A

Variant summary

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

The NM_024079.5(ALG8):c.95+23G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,552,016 control chromosomes in the GnomAD database, including 151,945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (12012 hom., cov: 34)
  • Exomes 𝑓: 0.44 (139933 hom.)
• Consequence: ALG8 NM_024079.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.789

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 11-78139471-C-A is Benign according to our data. Variant chr11-78139471-C-A is described in ClinVar as [Benign]. Clinvar id is 261685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG8	NM_024079.5	c.95+23G>T		intron_variant		ENST00000299626.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG8	ENST00000299626.10	c.95+23G>T		intron_variant		1	NM_024079.5	P3

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57696 AN: 152078 Hom.: 11999 Cov.: 34

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.391

GnomAD3 exomes AF: 0.423 AC: 66564 AN: 157346 Hom.: 14606 AF XY: 0.425 AC XY: 35312 AN XY: 83030

Gnomad AFR exome AF: 0.188

Gnomad AMR exome AF: 0.370

Gnomad ASJ exome AF: 0.415

Gnomad EAS exome AF: 0.373

Gnomad SAS exome AF: 0.414

Gnomad FIN exome AF: 0.548

Gnomad NFE exome AF: 0.460

Gnomad OTH exome AF: 0.434

GnomAD4 exome AF: 0.444 AC: 621005 AN: 1399820 Hom.: 139933 Cov.: 34 AF XY: 0.444 AC XY: 306637 AN XY: 690562

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.418

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.538

Gnomad4 NFE exome AF: 0.457

Gnomad4 OTH exome AF: 0.425

GnomAD4 genome AF: 0.379 AC: 57725 AN: 152196 Hom.: 12012 Cov.: 34 AF XY: 0.383 AC XY: 28522 AN XY: 74416

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.397

Alfa AF: 0.444 Hom.: 15351

Bravo AF: 0.358

Asia WGS AF: 0.424 AC: 1479 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

ALG8 congenital disorder of glycosylation Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	16
Dann	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.20		Position offset: 23

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

Publications

LitVar

Other links and lift over

dbSNP: rs10793289; hg19: chr11-77850517; COSMIC: COSV55199772; COSMIC: COSV55199772;