11-78101775-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001425224.1(ALG8):​c.1443-580T>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_001425224.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001425224.1. 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
	ALG8	NM_024079.5	MANE Select	c.1350-580T>C		intron	N/A	NP_076984.2
	ALG8	NM_001425224.1		c.1443-580T>C		intron	N/A	NP_001412153.1
	ALG8	NM_001425225.1		c.1398-580T>C		intron	N/A	NP_001412154.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG8	ENST00000299626.10	TSL:1 MANE Select	c.1350-580T>C		intron	N/A	ENSP00000299626.5
	ALG8	ENST00000679559.1		c.1350-580T>C		intron	N/A	ENSP00000505433.1
	ALG8	ENST00000532440.6	TSL:3	c.1398-580T>C		intron	N/A	ENSP00000433429.2

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

African (AFR) AF: 0.344 AC: 14274 AN: 41468

American (AMR) AF: 0.128 AC: 1957 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3470

East Asian (EAS) AF: 0.287 AC: 1488 AN: 5186

South Asian (SAS) AF: 0.201 AC: 969 AN: 4822

European-Finnish (FIN) AF: 0.0983 AC: 1043 AN: 10608

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10805 AN: 68010

Other (OTH) AF: 0.200 AC: 421 AN: 2110

Alfa AF: 0.104 Hom.: 169

Bravo AF: 0.217

Asia WGS AF: 0.224 AC: 781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.66
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs616892; hg19: chr11-77812821;