X-111744768-A-ACCT

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.2833_2835dupCCT(p.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 0.0207 in 575,972 control chromosomes in the GnomAD database, including 34 homozygotes. There are 1,089 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 19 hom., 71 hem., cov: 18)

Exomes 𝑓: 0.020 ( 15 hom. 1018 hem. )

Consequence

ALG13
NM_001099922.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

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:

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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-ACCT is Benign according to our data. Variant chrX-111744768-A-ACCT is described in ClinVar as Benign. ClinVar VariationId is 1168196.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 = 0.0369 (1365/37008) while in subpopulation NFE AF = 0.0508 (1007/19831). AF 95% confidence interval is 0.0482. There are 19 homozygotes in GnomAd4. There are 71 alleles in the male GnomAd4 subpopulation. Median coverage is 18. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG13	NM_001099922.3 link	c.2833_2835dupCCT	p.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.2833_2835dupCCT	p.Pro945dup	conservative_inframe_insertion	Exon 24 of 27	2	NM_001099922.3	ENSP00000378260.3		Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.0369

AC:

1365

AN:

37012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.0221

Gnomad AMR

AF:

0.0328

Gnomad ASJ

AF:

0.0180

Gnomad EAS

AF:

0.0141

Gnomad SAS

AF:

0.00926

Gnomad FIN

AF:

0.0790

Gnomad MID

AF:

0.0110

Gnomad NFE

AF:

0.0508

Gnomad OTH

AF:

0.0451

GnomAD2 exomes

AF:

0.0265

AC:

880

AN:

33243

AF XY:

0.00635

show subpopulations

Gnomad AFR exome

AF:

0.0132

Gnomad AMR exome

AF:

0.0243

Gnomad ASJ exome

AF:

0.0200

Gnomad EAS exome

AF:

0.0239

Gnomad FIN exome

AF:

0.0297

Gnomad NFE exome

AF:

0.0327

Gnomad OTH exome

AF:

0.0360

GnomAD4 exome

AF:

0.0196

AC:

10546

AN:

538964

Hom.:

Cov.:

AF XY:

0.00667

AC XY:

1018

AN XY:

152590

show subpopulations

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

African (AFR)

AF:

0.00694

AC:

AN:

14272

American (AMR)

AF:

0.0170

AC:

275

AN:

16198

Ashkenazi Jewish (ASJ)

AF:

0.0114

AC:

107

AN:

9360

East Asian (EAS)

AF:

0.00690

AC:

105

AN:

15209

South Asian (SAS)

AF:

0.00820

AC:

188

AN:

22917

European-Finnish (FIN)

AF:

0.0536

AC:

948

AN:

17686

Middle Eastern (MID)

AF:

0.0263

AC:

AN:

1481

European-Non Finnish (NFE)

AF:

0.0199

AC:

8304

AN:

418198

Other (OTH)

AF:

0.0203

AC:

481

AN:

23643

⚠️ 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: 0.365

Heterozygous variant carriers

440

880

1319

1759

2199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

250

500

750

1000

1250

<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:

0.0369

AC:

1365

AN:

37008

Hom.:

Cov.:

AF XY:

0.00997

AC XY:

AN XY:

7122

show subpopulations

African (AFR)

AF:

0.0116

AC:

115

AN:

9912

American (AMR)

AF:

0.0330

AC:

AN:

2514

Ashkenazi Jewish (ASJ)

AF:

0.0180

AC:

AN:

998

East Asian (EAS)

AF:

0.0141

AC:

AN:

1206

South Asian (SAS)

AF:

0.00931

AC:

AN:

537

European-Finnish (FIN)

AF:

0.0790

AC:

AN:

1190

Middle Eastern (MID)

AF:

0.0128

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0508

AC:

1007

AN:

19831

Other (OTH)

AF:

0.0424

AC:

AN:

425

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

118

176

235

294

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:

0.0180

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 08, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Significance:Likely 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.16

Mutation Taster

=88/12

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