Genetic Variant NM_024079.5: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_024079.5(ALG8):c.1349+1027_1349+1028delTT variant causes a 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. 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_024079.5 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.

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