Genetic Variant ALG8:c.1349+1028dupT (chr11-78102951-C-CA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001007027.3(ALG8):c.1350-4dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.011 ( 42 hom., cov: 0)

Exomes 𝑓: 0.045 ( 0 hom. )

Consequence

ALG8
NM_001007027.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.131

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007027.3. 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.1349+1028dupT	intron	N/A	NP_076984.2	A0A024R5K5
ALG8	NM_001425224.1		c.1442+1028dupT	intron	N/A	NP_001412153.1
ALG8	NM_001425225.1		c.1397+1028dupT	intron	N/A	NP_001412154.1	H0YDD3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALG8	ENST00000299626.10	TSL:1 MANE Select	c.1349+1028_1349+1029insT	intron	N/A	ENSP00000299626.5	Q9BVK2-1
ALG8	ENST00000679559.1		c.1349+1028_1349+1029insT	intron	N/A	ENSP00000505433.1	A0A7P0T919
ALG8	ENST00000532440.6	TSL:3	c.1397+1028_1397+1029insT	intron	N/A	ENSP00000433429.2	H0YDD3

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1281

AN:

118000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0581

Gnomad ASJ

AF:

0.00628

Gnomad EAS

AF:

0.0808

Gnomad SAS

AF:

0.00579

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.00410

Gnomad NFE

AF:

0.00135

Gnomad OTH

AF:

0.0155

GnomAD2 exomes

AF:

0.0556

AC:

AN:

126

AF XY:

0.0395

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0588

Gnomad ASJ exome

AF:

0.125

Gnomad NFE exome

AF:

0.0333

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.0451

AC:

AN:

1620

Hom.:

Cov.:

AF XY:

0.0444

AC XY:

AN XY:

1082

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0625

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0741

AC:

AN:

South Asian (SAS)

AF:

0.0102

AC:

AN:

European-Finnish (FIN)

AF:

0.0625

AC:

AN:

Middle Eastern (MID)

AF:

0.00565

AC:

AN:

354

European-Non Finnish (NFE)

AF:

0.0632

AC:

AN:

870

Other (OTH)

AF:

0.0566

AC:

AN:

106

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.362

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0108

AC:

1274

AN:

117986

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

692

AN XY:

56166

show subpopulations

African (AFR)

AF:

0.00221

AC:

AN:

32086

American (AMR)

AF:

0.0580

AC:

661

AN:

11404

Ashkenazi Jewish (ASJ)

AF:

0.00628

AC:

AN:

2868

East Asian (EAS)

AF:

0.0799

AC:

330

AN:

4128

South Asian (SAS)

AF:

0.00584

AC:

AN:

3598

European-Finnish (FIN)

AF:

0.0116

AC:

AN:

6368

Middle Eastern (MID)

AF:

0.00442

AC:

AN:

226

European-Non Finnish (NFE)

AF:

0.00135

AC:

AN:

54996

Other (OTH)

AF:

0.0149

AC:

AN:

1614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

148

197

246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.13

Mutation Taster

=100/0

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.

11-78102951-CAAAAAA-CAAAAAAA

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