chr11-78100944-T-C

Variant names:

• chr11-78100944-T-C
• rs1263505
• ENST00000925538.1:c.*20A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000925538.1(ALG8):​c.*20A>G variant causes a splice region 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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 ENST00000925538.1 splice_region
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.433
• Publications: 18 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):

• autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• ALG8-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• polycystic liver disease 3 with or without kidney cysts

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 96088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000925538.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG8	NM_024079.5	MANE Select	c.*20A>G		downstream_gene	N/A	NP_076984.2	A0A024R5K5
	ALG8	NM_001425224.1		c.*20A>G		downstream_gene	N/A	NP_001412153.1
	ALG8	NM_001425225.1		c.*20A>G		downstream_gene	N/A	NP_001412154.1	H0YDD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG8	ENST00000925538.1		c.*20A>G		splice_region	Exon 10 of 10	ENSP00000595597.1
	ALG8	ENST00000925534.1		c.*20A>G		splice_region	Exon 4 of 4	ENSP00000595593.1
	ALG8	ENST00000853767.1		c.*20A>G		3_prime_UTR	Exon 11 of 11	ENSP00000523826.1

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

GnomAD2 exomes AF: 0.823 AC: 206457 AN: 250820 AF XY: 0.828

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 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

African (AFR) AF: 0.941 AC: 31176 AN: 33146

American (AMR) AF: 0.703 AC: 31408 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 22652 AN: 26024

East Asian (EAS) AF: 0.695 AC: 27513 AN: 39604

South Asian (SAS) AF: 0.828 AC: 71132 AN: 85932

European-Finnish (FIN) AF: 0.837 AC: 44649 AN: 53330

Middle Eastern (MID) AF: 0.909 AC: 5215 AN: 5734

European-Non Finnish (NFE) AF: 0.845 AC: 928408 AN: 1098492

Other (OTH) AF: 0.847 AC: 50740 AN: 59918

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

African (AFR) AF: 0.936 AC: 38931 AN: 41582

American (AMR) AF: 0.759 AC: 11603 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3025 AN: 3470

East Asian (EAS) AF: 0.744 AC: 3848 AN: 5172

South Asian (SAS) AF: 0.826 AC: 3987 AN: 4828

European-Finnish (FIN) AF: 0.837 AC: 8883 AN: 10616

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57690 AN: 68006

Other (OTH) AF: 0.860 AC: 1817 AN: 2112

Alfa AF: 0.846 Hom.: 57052

Bravo AF: 0.856

Asia WGS AF: 0.802 AC: 2792 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	ALG8 congenital disorder of glycosylation (2)
-	-	2	not provided (2)
-	-	1	Congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		0.43
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1263505;

hg19: chr11-77811990;