X-111744768-ACCTCCTCCTCCTCCTCCTCCTCCT-ACCTCCT

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The NM_001099922.3(ALG13):c.2818_2835delCCTCCTCCTCCTCCTCCT(p.Pro940_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 0.000032 in 594,555 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P940P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., 0 hem., cov: 9)

Exomes 𝑓: 0.000029 ( 0 hom. 5 hem. )

Consequence

ALG13
NM_001099922.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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: Likely_benign. The variant received -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001099922.3

BS2

High Hemizygotes in GnomAdExome4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG13	NM_001099922.3 link	c.2818_2835delCCTCCTCCTCCTCCTCCT	p.Pro940_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.2818_2835delCCTCCTCCTCCTCCTCCT	p.Pro940_Pro945del	conservative_inframe_deletion	Exon 24 of 27	2	NM_001099922.3	ENSP00000378260.3		Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.0000807

AC:

AN:

37161

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000100

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000287

AC:

AN:

557394

Hom.:

AF XY:

0.0000315

AC XY:

AN XY:

158562

show subpopulations

African (AFR)

AF:

0.000138

AC:

AN:

14463

American (AMR)

AF:

0.0000605

AC:

AN:

16521

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9525

East Asian (EAS)

AF:

0.00

AC:

AN:

15385

South Asian (SAS)

AF:

0.0000424

AC:

AN:

23599

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1547

European-Non Finnish (NFE)

AF:

0.0000277

AC:

AN:

433347

Other (OTH)

AF:

0.00

AC:

AN:

24413

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

0.0000807

AC:

AN:

37161

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

7145

show subpopulations

African (AFR)

AF:

0.000101

AC:

AN:

9937

American (AMR)

AF:

0.00

AC:

AN:

2509

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:

540

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000100

AC:

AN:

19920

Other (OTH)

AF:

0.00

AC:

AN:

425

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 36

Uncertain:1

Oct 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant, c.2818_2835del, results in the deletion of 6 amino acid(s) of the ALG13 protein (p.Pro940_Pro945del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ALG13-related conditions. This variant has been observed to be homozygous, hemizygous or homoplasmic in an individual who did not have the expected clinical features for that genetic result (internal data). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.32

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over