chr11-78101038-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024079.5(ALG8):c.1507A>G(p.Ile503Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000815 in 1,614,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00086 ( 0 hom. )

Consequence

ALG8
NM_024079.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:7

Conservation

PhyloP100: 0.483

Publications

10 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: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, G2P, 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023552626).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALG8	NM_024079.5	MANE Select	c.1507A>G	p.Ile503Val	missense	Exon 13 of 13	NP_076984.2	A0A024R5K5
ALG8	NM_001425224.1		c.1600A>G	p.Ile534Val	missense	Exon 14 of 14	NP_001412153.1
ALG8	NM_001425225.1		c.1555A>G	p.Ile519Val	missense	Exon 14 of 14	NP_001412154.1	H0YDD3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALG8	ENST00000299626.10	TSL:1 MANE Select	c.1507A>G	p.Ile503Val	missense	Exon 13 of 13	ENSP00000299626.5	Q9BVK2-1
ALG8	ENST00000532440.6	TSL:3	c.1555A>G	p.Ile519Val	missense	Exon 14 of 14	ENSP00000433429.2	H0YDD3
ALG8	ENST00000853774.1		c.1528A>G	p.Ile510Val	missense	Exon 13 of 13	ENSP00000523833.1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000493

AC:

124

AN:

251366

AF XY:

0.000574

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000871

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000860

AC:

1257

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000850

AC XY:

618

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33480

American (AMR)

AF:

0.000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00153

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00106

AC:

1181

AN:

1112004

Other (OTH)

AF:

0.000331

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

143

214

286

357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000387

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41578

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000676

AC:

AN:

68028

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000846

Hom.:

Bravo

AF:

0.000423

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000576

AC:

EpiCase

AF:

0.00115

EpiControl

AF:

0.00166

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

ALG8 congenital disorder of glycosylation (1)

ALG8 congenital disorder of glycosylation;C4693472:Polycystic liver disease 3 with or without kidney cysts (1)

ALG8-related disorder (1)

Polycystic liver disease 3 with or without kidney cysts (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.28

CADD

Benign

7.7

(source)

DANN

Benign

0.39

DEOGEN2

Benign

0.12

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.72

M_CAP

Benign

0.011

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.87

MutationAssessor

Benign

-0.52

PhyloP100

0.48

PrimateAI

Benign

0.36

PROVEAN

Benign

0.35

REVEL

Benign

0.23

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.14

MVP

0.47

MPC

0.12

ClinPred

0.0025

GERP RS

0.093

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.012

gMVP

0.19

Mutation Taster

=94/6

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over