11-78100847-T-C

Position:

• chr11-78100847-T-C

Variant summary

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

The ENST00000679559.1(ALG8):​c.1452+246A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 929,880 control chromosomes in the GnomAD database, including 2,349 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (329 hom., cov: 34)
  • Exomes 𝑓: 0.067 (2020 hom.)
• Consequence: ALG8 ENST00000679559.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0700

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=-0.76).
• BP6: Variant 11-78100847-T-C is Benign according to our data. Variant chr11-78100847-T-C is described in ClinVar as [Benign]. Clinvar id is 1255268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0766 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+246A>G		intron_variant				ENSP00000505433.1
ALG8	ENST00000680398.1	c.1452+246A>G		intron_variant				ENSP00000506189.1

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 8273 AN: 152210 Hom.: 330 Cov.: 34

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0455

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0432

Gnomad FIN AF: 0.0967

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.0660

GnomAD4 exome AF: 0.0666 AC: 51792 AN: 777552 Hom.: 2020 AF XY: 0.0659 AC XY: 26763 AN XY: 406374

Gnomad4 AFR exome AF: 0.0125

Gnomad4 AMR exome AF: 0.0330

Gnomad4 ASJ exome AF: 0.0770

Gnomad4 EAS exome AF: 0.000201

Gnomad4 SAS exome AF: 0.0452

Gnomad4 FIN exome AF: 0.0932

Gnomad4 NFE exome AF: 0.0758

Gnomad4 OTH exome AF: 0.0668

GnomAD4 genome AF: 0.0543 AC: 8267 AN: 152328 Hom.: 329 Cov.: 34 AF XY: 0.0535 AC XY: 3987 AN XY: 74490

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0454

Gnomad4 ASJ AF: 0.0847

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0427

Gnomad4 FIN AF: 0.0967

Gnomad4 NFE AF: 0.0784

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.0707 Hom.: 81

Bravo AF: 0.0485

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11237385; hg19: chr11-77811893;