X-111744768-A-ACCTCCT

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The NM_001099922.3(ALG13):c.2830_2835dupCCTCCT(p.Pro944_Pro945dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000419 in 594,036 control chromosomes in the GnomAD database, including 1 homozygotes. There are 31 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00094 ( 0 hom., 1 hem., cov: 18)

Exomes 𝑓: 0.00038 ( 1 hom. 30 hem. )

Consequence

ALG13
NM_001099922.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.159

Publications

3 publications found

Variant links:

Genes affected

ALG13 (HGNC:30881): (ALG13 UDP-N-acetylglucosaminyltransferase subunit) The protein encoded by this gene is a subunit of a bipartite UDP-N-acetylglucosamine transferase. It heterodimerizes with asparagine-linked glycosylation 14 homolog to form a functional UDP-GlcNAc glycosyltransferase that catalyzes the second sugar addition of the highly conserved oligosaccharide precursor in endoplasmic reticulum N-linked glycosylation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

ALG13 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy, 36
Inheritance: XL Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ALG13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001099922.3

BP6

Variant X-111744768-A-ACCTCCT is Benign according to our data. Variant chrX-111744768-A-ACCTCCT is described in ClinVar as Likely_benign. ClinVar VariationId is 700610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000942 (35/37147) while in subpopulation NFE AF = 0.00136 (27/19912). AF 95% confidence interval is 0.000956. There are 0 homozygotes in GnomAd4. There are 1 alleles in the male GnomAd4 subpopulation. Median coverage is 18. This position passed quality control check.

BS2

High Hemizygotes in GnomAdExome4 at 30 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG13	NM_001099922.3 link	c.2830_2835dupCCTCCT	p.Pro944_Pro945dup	conservative_inframe_insertion	Exon 24 of 27	ENST00000394780.8	NP_001093392.1	Q9NP73-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG13	ENST00000394780.8 link	c.2830_2835dupCCTCCT	p.Pro944_Pro945dup	conservative_inframe_insertion	Exon 24 of 27	2	NM_001099922.3	ENSP00000378260.3		Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.000942

AC:

AN:

37151

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000503

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000797

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0110

Gnomad NFE

AF:

0.00136

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000692

AC:

AN:

33243

AF XY:

0.000176

show subpopulations

Gnomad AFR exome

AF:

0.000714

Gnomad AMR exome

AF:

0.000957

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000384

AC:

214

AN:

556889

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

158355

show subpopulations

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

African (AFR)

AF:

0.000346

AC:

AN:

14454

American (AMR)

AF:

0.000727

AC:

AN:

16512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9522

East Asian (EAS)

AF:

0.000325

AC:

AN:

15380

South Asian (SAS)

AF:

0.000255

AC:

AN:

23572

European-Finnish (FIN)

AF:

0.0000538

AC:

AN:

18588

Middle Eastern (MID)

AF:

0.000648

AC:

AN:

1544

European-Non Finnish (NFE)

AF:

0.000404

AC:

175

AN:

432923

Other (OTH)

AF:

0.000369

AC:

AN:

24394

⚠️ 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: 0.354

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000942

AC:

AN:

37147

Hom.:

Cov.:

AF XY:

0.000140

AC XY:

AN XY:

7145

show subpopulations

African (AFR)

AF:

0.000503

AC:

AN:

9934

American (AMR)

AF:

0.000794

AC:

AN:

2520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1002

East Asian (EAS)

AF:

0.00

AC:

AN:

1208

South Asian (SAS)

AF:

0.00

AC:

AN:

535

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1212

Middle Eastern (MID)

AF:

0.0128

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00136

AC:

AN:

19912

Other (OTH)

AF:

0.00

AC:

AN:

429

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00172

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Mar 27, 2024

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Developmental and epileptic encephalopathy, 36

Benign:1

Dec 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ALG13-related disorder

Benign:1

Jan 08, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ALG13: BP3 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.16

Mutation Taster

=89/11

polymorphism

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over