Genetic Variant ALG8:c.1349+1027_1349+1028delTT (chr11-78102951-CAA-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_001007027.3(ALG8):c.1350-5_1350-4delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0425 in 119,654 control chromosomes in the GnomAD database, including 163 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.042 ( 163 hom., cov: 0)

Exomes 𝑓: 0.10 ( 0 hom. )

Consequence

ALG8
NM_001007027.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: 0.131

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 11-78102951-CAA-C is Benign according to our data. Variant chr11-78102951-CAA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1205867.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-78102951-CAA-C is described in Lovd as [Benign]. Variant chr11-78102951-CAA-C is described in Lovd as [Likely_benign]. Variant chr11-78102951-CAA-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG8	NM_024079.5 link	c.1349+1027_1349+1028delTT		intron_variant	Intron 12 of 12	ENST00000299626.10	NP_076984.2	Q9BVK2-1A0A024R5K5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG8	ENST00000299626.10 link	c.1349+1027_1349+1028delTT		intron_variant	Intron 12 of 12	1	NM_024079.5	ENSP00000299626.5		Q9BVK2-1

Frequencies

GnomAD3 genomes

AF:

0.0417

AC:

4918

AN:

118048

Hom.:

163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0582

Gnomad ASJ

AF:

0.00384

Gnomad EAS

AF:

0.0681

Gnomad SAS

AF:

0.0146

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.00410

Gnomad NFE

AF:

0.00720

Gnomad OTH

AF:

0.0285

GnomAD3 exomes

AF:

0.0794

AC:

AN:

126

Hom.:

AF XY:

0.0921

AC XY:

AN XY:

show subpopulations

Gnomad AFR exome

AF:

0.125

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad SAS exome

AF:

0.250

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.101

AC:

163

AN:

1618

Hom.:

AF XY:

0.0891

AC XY:

AN XY:

1078

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.0313

Gnomad4 ASJ exome

AF:

0.0455

Gnomad4 EAS exome

AF:

0.0741

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.188

Gnomad4 NFE exome

AF:

0.0908

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.0417

AC:

4918

AN:

118036

Hom.:

163

Cov.:

AF XY:

0.0424

AC XY:

2379

AN XY:

56172

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.0583

Gnomad4 ASJ

AF:

0.00384

Gnomad4 EAS

AF:

0.0677

Gnomad4 SAS

AF:

0.0145

Gnomad4 FIN

AF:

0.0132

Gnomad4 NFE

AF:

0.00720

Gnomad4 OTH

AF:

0.0285

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not specified

Benign:1

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

11-78102951-CAAAAAA-CAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over