Genetic Variant ALG8:c.1349+1027_1349+1028dupTT (chr11-78102951-C-CAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001007027.3(ALG8):c.1350-5_1350-4dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000076 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0062 ( 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: Uncertain_significance. The variant received 0 ACMG points.

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+1027_1349+1028dupTT	intron	N/A	NP_076984.2	A0A024R5K5
ALG8	NM_001425224.1		c.1442+1027_1442+1028dupTT	intron	N/A	NP_001412153.1
ALG8	NM_001425225.1		c.1397+1027_1397+1028dupTT	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+1029insTT	intron	N/A	ENSP00000299626.5	Q9BVK2-1
ALG8	ENST00000679559.1		c.1349+1028_1349+1029insTT	intron	N/A	ENSP00000505433.1	A0A7P0T919
ALG8	ENST00000532440.6	TSL:3	c.1397+1028_1397+1029insTT	intron	N/A	ENSP00000433429.2	H0YDD3

Frequencies

GnomAD3 genomes

AF:

0.0000762

AC:

AN:

118046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000936

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000241

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000157

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000182

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0159

AC:

AN:

126

AF XY:

0.0263

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0294

Gnomad ASJ exome

AF:

0.00

Gnomad NFE exome

AF:

0.0167

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00616

AC:

AN:

1624

Hom.:

Cov.:

AF XY:

0.00738

AC XY:

AN XY:

1084

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:

0.0156

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0370

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

354

European-Non Finnish (NFE)

AF:

0.00688

AC:

AN:

872

Other (OTH)

AF:

0.00943

AC:

AN:

106

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000249944), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.330

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000762

AC:

AN:

118034

Hom.:

Cov.:

AF XY:

0.0000890

AC XY:

AN XY:

56182

show subpopulations

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

African (AFR)

AF:

0.0000935

AC:

AN:

32086

American (AMR)

AF:

0.000263

AC:

AN:

11422

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2868

East Asian (EAS)

AF:

0.000242

AC:

AN:

4134

South Asian (SAS)

AF:

0.00

AC:

AN:

3598

European-Finnish (FIN)

AF:

0.000157

AC:

AN:

6372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

226

European-Non Finnish (NFE)

AF:

0.0000182

AC:

AN:

55016

Other (OTH)

AF:

0.00

AC:

AN:

1614

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000850349), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.358

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.13

Mutation Taster

=96/4

polymorphism

(source)

Splicing

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-CAAAAAAAA

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