11-78101775-A-G

Variant names:

• chr11-78101775-A-G
• rs616892
• NM_024079.5:c.1350-580T>C

Variant summary

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

The NM_024079.5(ALG8):​c.1350-580T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,174 control chromosomes in the GnomAD database, including 3,911 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 0.21 (3911 hom., cov: 33)
• Consequence: ALG8 NM_024079.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG8	NM_024079.5	c.1350-580T>C		intron_variant	Intron 12 of 12	ENST00000299626.10	NP_076984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG8	ENST00000299626.10	c.1350-580T>C		intron_variant	Intron 12 of 12	1	NM_024079.5	ENSP00000299626.5

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31722 AN: 152056 Hom.: 3909 Cov.: 33

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.0983

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.209 AC: 31746 AN: 152174 Hom.: 3911 Cov.: 33 AF XY: 0.204 AC XY: 15185 AN XY: 74404

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.0983

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.200

Alfa AF: 0.0914 Hom.: 123

Bravo AF: 0.217

Asia WGS AF: 0.224 AC: 781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.66

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: rs616892; hg19: chr11-77812821;