rs1789032

Variant names:

• chr11-78109627-T-C
• rs1789032
• NM_024079.5:c.899-46A>G

Variant summary

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

The NM_024079.5(ALG8):​c.899-46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,525,356 control chromosomes in the GnomAD database, including 26,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4389 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21919 hom.)
• Consequence: ALG8 NM_024079.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.13
• Publications: 8 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• polycystic liver disease 3 with or without kidney cysts

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-78109627-T-C is Benign according to our data. Variant chr11-78109627-T-C is described in ClinVar as Benign. ClinVar VariationId is 261684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024079.5. 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.899-46A>G		intron	N/A	NP_076984.2	A0A024R5K5
	ALG8	NM_001425224.1		c.992-46A>G		intron	N/A	NP_001412153.1
	ALG8	NM_001425225.1		c.899-46A>G		intron	N/A	NP_001412154.1	H0YDD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG8	ENST00000299626.10	TSL:1 MANE Select	c.899-46A>G		intron	N/A	ENSP00000299626.5	Q9BVK2-1
	ALG8	ENST00000679559.1		c.899-46A>G		intron	N/A	ENSP00000505433.1	A0A7P0T919
	ALG8	ENST00000532440.6	TSL:3	c.899-46A>G		intron	N/A	ENSP00000433429.2	H0YDD3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33031 AN: 151834 Hom.: 4386 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0976

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.203

GnomAD2 exomes AF: 0.180 AC: 43102 AN: 238798 AF XY: 0.180

Gnomad AFR exome AF: 0.389

Gnomad AMR exome AF: 0.0937

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.301

Gnomad FIN exome AF: 0.109

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.171 AC: 235473 AN: 1373408 Hom.: 21919 Cov.: 23 AF XY: 0.171 AC XY: 117914 AN XY: 687938

African (AFR) AF: 0.397 AC: 12561 AN: 31648

American (AMR) AF: 0.0979 AC: 4322 AN: 44150

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 3933 AN: 25506

East Asian (EAS) AF: 0.300 AC: 11631 AN: 38808

South Asian (SAS) AF: 0.213 AC: 17905 AN: 83874

European-Finnish (FIN) AF: 0.115 AC: 6057 AN: 52820

Middle Eastern (MID) AF: 0.247 AC: 1380 AN: 5594

European-Non Finnish (NFE) AF: 0.161 AC: 166793 AN: 1033522

Other (OTH) AF: 0.189 AC: 10891 AN: 57486

GnomAD4 genome AF: 0.218 AC: 33053 AN: 151948 Hom.: 4389 Cov.: 32 AF XY: 0.212 AC XY: 15769 AN XY: 74276

African (AFR) AF: 0.379 AC: 15654 AN: 41326

American (AMR) AF: 0.130 AC: 1991 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 550 AN: 3472

East Asian (EAS) AF: 0.284 AC: 1465 AN: 5164

South Asian (SAS) AF: 0.201 AC: 967 AN: 4818

European-Finnish (FIN) AF: 0.0976 AC: 1035 AN: 10608

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

European-Non Finnish (NFE) AF: 0.158 AC: 10746 AN: 67952

Other (OTH) AF: 0.201 AC: 424 AN: 2112

Alfa AF: 0.193 Hom.: 636

Bravo AF: 0.229

Asia WGS AF: 0.226 AC: 786 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.031
DANN	Benign	0.41
PhyloP100		-3.1
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: rs1789032; hg19: chr11-77820673; COSMIC: COSV55199070; COSMIC: COSV55199070;