X-111744768-ACCTCCTCCTCCTCCTCCTCCTCCT-ACCTCCTCCTCCTCCTCCTCCT

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_001099922.3(ALG13):c.2833_2835delCCT(p.Pro945del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 455,685 control chromosomes in the GnomAD database, including 65 homozygotes. There are 1,205 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P945P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.038 ( 35 hom., 64 hem., cov: 9)

Exomes 𝑓: 0.049 ( 30 hom. 1141 hem. )

Consequence

ALG13
NM_001099922.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

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-ACCT-A is Benign according to our data. Variant chrX-111744768-ACCT-A is described in ClinVar as Benign. ClinVar VariationId is 238295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG13	NM_001099922.3 link	c.2833_2835delCCT	p.Pro945del	conservative_inframe_deletion	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.2833_2835delCCT	p.Pro945del	conservative_inframe_deletion	Exon 24 of 27	2	NM_001099922.3	ENSP00000378260.3		Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.0378

AC:

1398

AN:

37019

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0205

Gnomad ASJ

AF:

0.0299

Gnomad EAS

AF:

0.00995

Gnomad SAS

AF:

0.0167

Gnomad FIN

AF:

0.00338

Gnomad MID

AF:

0.0330

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.0447

GnomAD2 exomes

AF:

0.0951

AC:

3160

AN:

33243

AF XY:

0.0120

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.120

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.132

Gnomad FIN exome

AF:

0.0548

Gnomad NFE exome

AF:

0.0709

Gnomad OTH exome

AF:

0.0941

GnomAD4 exome

AF:

0.0493

AC:

20634

AN:

418670

Hom.:

AF XY:

0.0109

AC XY:

1141

AN XY:

104424

show subpopulations

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

African (AFR)

AF:

0.138

AC:

1526

AN:

11048

American (AMR)

AF:

0.0731

AC:

900

AN:

12310

Ashkenazi Jewish (ASJ)

AF:

0.0837

AC:

515

AN:

6151

East Asian (EAS)

AF:

0.0619

AC:

538

AN:

8689

South Asian (SAS)

AF:

0.0550

AC:

863

AN:

15680

European-Finnish (FIN)

AF:

0.0309

AC:

372

AN:

12032

Middle Eastern (MID)

AF:

0.0426

AC:

AN:

1103

European-Non Finnish (NFE)

AF:

0.0444

AC:

14862

AN:

334505

Other (OTH)

AF:

0.0589

AC:

1011

AN:

17152

⚠️ 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: 0.312

Heterozygous variant carriers

1736

3473

5209

6946

8682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

646

1292

1938

2584

3230

<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:

0.0377

AC:

1397

AN:

37015

Hom.:

Cov.:

AF XY:

0.00898

AC XY:

AN XY:

7127

show subpopulations

African (AFR)

AF:

0.102

AC:

1004

AN:

9872

American (AMR)

AF:

0.0204

AC:

AN:

2502

Ashkenazi Jewish (ASJ)

AF:

0.0299

AC:

AN:

1002

East Asian (EAS)

AF:

0.00995

AC:

AN:

1206

South Asian (SAS)

AF:

0.0168

AC:

AN:

537

European-Finnish (FIN)

AF:

0.00338

AC:

AN:

1184

Middle Eastern (MID)

AF:

0.0256

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0133

AC:

265

AN:

19888

Other (OTH)

AF:

0.0466

AC:

AN:

429

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

104

156

208

260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0255

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy, 36

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Apr 19, 2022

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as 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. -

ALG13-related disorder

Benign:1

Jan 05, 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

Oct 21, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.16

Mutation Taster

=92/8

polymorphism (auto)

(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