rs11237385

Variant names:

• chr11-78100847-T-C
• rs11237385
• ENST00000853767.1:c.*117A>G

Variant summary

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

The ENST00000853767.1(ALG8):​c.*117A>G variant causes a 3 prime UTR 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 ENST00000853767.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0700
• Publications: 7 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=-0.76).
• BP6: Variant 11-78100847-T-C is Benign according to our data. Variant chr11-78100847-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000853767.1. 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.*117A>G		downstream_gene	N/A	NP_076984.2	A0A024R5K5
	ALG8	NM_001425224.1		c.*117A>G		downstream_gene	N/A	NP_001412153.1
	ALG8	NM_001425225.1		c.*117A>G		downstream_gene	N/A	NP_001412154.1	H0YDD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG8	ENST00000853767.1		c.*117A>G		3_prime_UTR	Exon 11 of 11	ENSP00000523826.1
	ALG8	ENST00000679559.1		c.1452+246A>G		intron	N/A	ENSP00000505433.1	A0A7P0T919
	ALG8	ENST00000680398.1		c.1452+246A>G		intron	N/A	ENSP00000506189.1	A0A7P0TAL7

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

African (AFR) AF: 0.0125 AC: 253 AN: 20286

American (AMR) AF: 0.0330 AC: 1202 AN: 36446

Ashkenazi Jewish (ASJ) AF: 0.0770 AC: 1593 AN: 20686

East Asian (EAS) AF: 0.000201 AC: 7 AN: 34882

South Asian (SAS) AF: 0.0452 AC: 3032 AN: 67040

European-Finnish (FIN) AF: 0.0932 AC: 3671 AN: 39378

Middle Eastern (MID) AF: 0.0717 AC: 204 AN: 2844

European-Non Finnish (NFE) AF: 0.0758 AC: 39323 AN: 518464

Other (OTH) AF: 0.0668 AC: 2507 AN: 37526

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

African (AFR) AF: 0.0129 AC: 537 AN: 41578

American (AMR) AF: 0.0454 AC: 695 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0427 AC: 206 AN: 4830

European-Finnish (FIN) AF: 0.0967 AC: 1027 AN: 10616

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0784 AC: 5334 AN: 68040

Other (OTH) AF: 0.0653 AC: 138 AN: 2114

Alfa AF: 0.0537 Hom.: 139

Bravo AF: 0.0485

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.59
PhyloP100		-0.070
Mutation Taster		=98/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs11237385; hg19: chr11-77811893;