chrX-111744768-ACCTCCTCCTCCT-A

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.2824_2835delCCTCCTCCTCCT(p.Pro942_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 0.000456 in 594,412 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 82 hemizygotes in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., 4 hem., cov: 9)

Exomes 𝑓: 0.00043 ( 0 hom. 78 hem. )

Consequence

ALG13
NM_001099922.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.322

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-ACCTCCTCCTCCT-A is Benign according to our data. Variant chrX-111744768-ACCTCCTCCTCCT-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 516988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000861 (32/37156) while in subpopulation AMR AF = 0.00278 (7/2520). AF 95% confidence interval is 0.0013. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 9. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG13	NM_001099922.3 link	c.2824_2835delCCTCCTCCTCCT	p.Pro942_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.2824_2835delCCTCCTCCTCCT	p.Pro942_Pro945del	conservative_inframe_deletion	Exon 24 of 27	2	NM_001099922.3	ENSP00000378260.3		Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.000861

AC:

AN:

37160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00279

Gnomad ASJ

AF:

0.00599

Gnomad EAS

AF:

0.00248

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000825

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000703

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000993

AC:

AN:

33243

AF XY:

0.00106

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000957

Gnomad ASJ exome

AF:

0.00451

Gnomad EAS exome

AF:

0.000758

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000762

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000429

AC:

239

AN:

557256

Hom.:

AF XY:

0.000492

AC XY:

AN XY:

158534

show subpopulations

African (AFR)

AF:

0.0000692

AC:

AN:

14460

American (AMR)

AF:

0.000545

AC:

AN:

16514

Ashkenazi Jewish (ASJ)

AF:

0.00347

AC:

AN:

9520

East Asian (EAS)

AF:

0.00104

AC:

AN:

15381

South Asian (SAS)

AF:

0.000678

AC:

AN:

23590

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

18591

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1547

European-Non Finnish (NFE)

AF:

0.000323

AC:

140

AN:

433247

Other (OTH)

AF:

0.000697

AC:

AN:

24406

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

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:

0.000861

AC:

AN:

37156

Hom.:

Cov.:

AF XY:

0.000560

AC XY:

AN XY:

7144

show subpopulations

African (AFR)

AF:

0.000101

AC:

AN:

9936

American (AMR)

AF:

0.00278

AC:

AN:

2520

Ashkenazi Jewish (ASJ)

AF:

0.00599

AC:

AN:

1002

East Asian (EAS)

AF:

0.00248

AC:

AN:

1208

South Asian (SAS)

AF:

0.00

AC:

AN:

537

European-Finnish (FIN)

AF:

0.000825

AC:

AN:

1212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000703

AC:

AN:

19918

Other (OTH)

AF:

0.00

AC:

AN:

428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.000409

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ALG13-related disorder

Benign:1

Feb 23, 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 12, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.32

Mutation Taster

=197/3

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