Genetic Variant ALG8:c.*147G>A (chr11-78100817-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The ENST00000853767.1(ALG8):c.*147G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00611 in 721,560 control chromosomes in the GnomAD database, including 148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 103 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 45 hom. )

Consequence

ALG8
ENST00000853767.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.961

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 11-78100817-C-T is Benign according to our data. Variant chr11-78100817-C-T is described in ClinVar as Benign. ClinVar VariationId is 1286202.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0672 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALG8	NM_024079.5	MANE Select	c.*147G>A	downstream_gene	N/A	NP_076984.2	A0A024R5K5
ALG8	NM_001425224.1		c.*147G>A	downstream_gene	N/A	NP_001412153.1
ALG8	NM_001425225.1		c.*147G>A	downstream_gene	N/A	NP_001412154.1	H0YDD3

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
ALG8	ENST00000853767.1	c.*147G>A	3_prime_UTR	Exon 11 of 11	ENSP00000523826.1
ALG8	ENST00000679559.1	c.1452+276G>A	intron	N/A	ENSP00000505433.1	A0A7P0T919
ALG8	ENST00000680398.1	c.1452+276G>A	intron	N/A	ENSP00000506189.1	A0A7P0TAL7

Frequencies

GnomAD3 genomes

AF:

0.0198

AC:

3018

AN:

152152

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0695

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00662

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0115

GnomAD4 exome

AF:

0.00244

AC:

1388

AN:

569288

Hom.:

AF XY:

0.00202

AC XY:

605

AN XY:

299688

show subpopulations

African (AFR)

AF:

0.0701

AC:

1103

AN:

15728

American (AMR)

AF:

0.00321

AC:

AN:

30544

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17188

East Asian (EAS)

AF:

0.0000312

AC:

AN:

32010

South Asian (SAS)

AF:

0.000235

AC:

AN:

55214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32834

Middle Eastern (MID)

AF:

0.00259

AC:

AN:

2318

European-Non Finnish (NFE)

AF:

0.000102

AC:

AN:

352922

Other (OTH)

AF:

0.00429

AC:

131

AN:

30530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

134

202

269

336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0198

AC:

3019

AN:

152272

Hom.:

103

Cov.:

AF XY:

0.0187

AC XY:

1395

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0693

AC:

2878

AN:

41530

American (AMR)

AF:

0.00661

AC:

101

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000220

AC:

AN:

68040

Other (OTH)

AF:

0.0113

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

143

286

428

571

714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0130

Hom.:

Bravo

AF:

0.0220

Asia WGS

AF:

0.00433

AC:

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

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

0.96

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over