11-78100748-GT-GTTT

Variant names:

• chr11-78100748-G-GTT
• rs3841745
• ENST00000853767.1:c.*214_*215dupAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000853767.1(ALG8):​c.*214_*215dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,002 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 28)
• Consequence: ALG8 ENST00000853767.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.908
• 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):

• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.*215_*216insAA		downstream_gene	N/A	NP_076984.2	A0A024R5K5
	ALG8	NM_001425224.1		c.*215_*216insAA		downstream_gene	N/A	NP_001412153.1
	ALG8	NM_001425225.1		c.*215_*216insAA		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.*214_*215dupAA		3_prime_UTR	Exon 11 of 11	ENSP00000523826.1
	ALG8	ENST00000679559.1		c.1452+343_1452+344dupAA		intron	N/A	ENSP00000505433.1	A0A7P0T919
	ALG8	ENST00000680398.1		c.1452+343_1452+344dupAA		intron	N/A	ENSP00000506189.1	A0A7P0TAL7

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152002 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152002 Hom.: 0 Cov.: 28 AF XY: 0.0000135 AC XY: 1 AN XY: 74242

African (AFR) AF: 0.0000242 AC: 1 AN: 41366

American (AMR) AF: 0.00 AC: 0 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 83

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.91

Splicing

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

Other links and lift over

dbSNP: rs3841745; hg19: chr11-77811794;