Genetic Variant ENST00000679559.1:c.1452+344_1452+345insA (chr11-78100748-G-GT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000679559.1(ALG8):c.1452+344dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,058 control chromosomes in the GnomAD database, including 3,906 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.21 ( 3906 hom., cov: 28)

Consequence

ALG8
ENST00000679559.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.908

Publications

2 publications found

Variant links:

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

ALG8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 11-78100748-G-GT is Benign according to our data. Variant chr11-78100748-G-GT is described in ClinVar as Benign. ClinVar VariationId is 1235083.Status of the report is criteria_provided_single_submitter, 1 stars.

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: ENST00000679559.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALG8	NM_024079.5	MANE Select	c.215_216insA	downstream_gene	N/A	NP_076984.2	A0A024R5K5
ALG8	NM_001425224.1		c.215_216insA	downstream_gene	N/A	NP_001412153.1
ALG8	NM_001425225.1		c.215_216insA	downstream_gene	N/A	NP_001412154.1	H0YDD3

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
ALG8	ENST00000853767.1	c.*215dupA	3_prime_UTR	Exon 11 of 11	ENSP00000523826.1
ALG8	ENST00000679559.1	c.1452+344dupA	intron	N/A	ENSP00000505433.1	A0A7P0T919
ALG8	ENST00000680398.1	c.1452+344dupA	intron	N/A	ENSP00000506189.1	A0A7P0TAL7

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31678

AN:

151940

Hom.:

3904

Cov.:

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.285

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.0981

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:

0.208

AC:

31702

AN:

152058

Hom.:

3906

Cov.:

AF XY:

0.204

AC XY:

15143

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.344

AC:

14258

AN:

41452

American (AMR)

AF:

0.128

AC:

1954

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

565

AN:

3468

East Asian (EAS)

AF:

0.285

AC:

1473

AN:

5164

South Asian (SAS)

AF:

0.201

AC:

967

AN:

4806

European-Finnish (FIN)

AF:

0.0981

AC:

1039

AN:

10594

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10802

AN:

67996

Other (OTH)

AF:

0.200

AC:

421

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1213

2427

3640

4854

6067

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0743

Hom.:

Bravo

AF:

0.216

Asia WGS

AF:

0.224

AC:

779

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over