Genetic Variant ALG8:c.1349+1023_1349+1028delTTTTTT (chr11-78102951-CAAAAAA-C) – 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.1350-9_1350-4delTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,628 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0012 ( 0 hom. )

Consequence

ALG8
NM_001007027.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.730

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: 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+1023_1349+1028delTTTTTT	intron	N/A	NP_076984.2	A0A024R5K5
ALG8	NM_001425224.1		c.1442+1023_1442+1028delTTTTTT	intron	N/A	NP_001412153.1
ALG8	NM_001425225.1		c.1397+1023_1397+1028delTTTTTT	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+1023_1349+1028delTTTTTT	intron	N/A	ENSP00000299626.5	Q9BVK2-1
ALG8	ENST00000679559.1		c.1349+1023_1349+1028delTTTTTT	intron	N/A	ENSP00000505433.1	A0A7P0T919
ALG8	ENST00000532440.6	TSL:3	c.1397+1023_1397+1028delTTTTTT	intron	N/A	ENSP00000433429.2	H0YDD3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00123

AC:

AN:

1628

Hom.:

AF XY:

0.00

AC XY:

AN XY:

1086

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:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

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:

0.00228

AC:

AN:

876

Other (OTH)

AF:

0.00

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: 0.250

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.73

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over