rs747478031

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001099922.3(ALG13):c.1304A>G(p.Asn435Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,186,141 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N435K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.000042 ( 0 hom. 8 hem. )

Consequence

ALG13
NM_001099922.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -0.420

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073872507).

BP6

Variant X-111720148-A-G is Benign according to our data. Variant chrX-111720148-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 373473.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000446 (5/112061) while in subpopulation AMR AF = 0.000472 (5/10595). AF 95% confidence interval is 0.000185. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 23. 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.1304A>G	p.Asn435Ser	missense_variant	Exon 11 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.1304A>G	p.Asn435Ser	missense_variant	Exon 11 of 27	2	NM_001099922.3	ENSP00000378260.3		Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.0000446

AC:

AN:

112009

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000472

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000207

AC:

AN:

149947

AF XY:

0.000113

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00132

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000419

AC:

AN:

1074080

Hom.:

Cov.:

AF XY:

0.0000233

AC XY:

AN XY:

343352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25720

American (AMR)

AF:

0.00116

AC:

AN:

32739

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18790

East Asian (EAS)

AF:

0.00

AC:

AN:

29787

South Asian (SAS)

AF:

0.00

AC:

AN:

49843

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39697

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4045

European-Non Finnish (NFE)

AF:

0.00000845

AC:

AN:

828207

Other (OTH)

AF:

0.00

AC:

AN:

45252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

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:

0.0000446

AC:

AN:

112061

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34211

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30836

American (AMR)

AF:

0.000472

AC:

AN:

10595

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.00

AC:

AN:

3572

South Asian (SAS)

AF:

0.00

AC:

AN:

2700

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6088

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53199

Other (OTH)

AF:

0.00

AC:

AN:

1527

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000524

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.000168

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:1

Nov 05, 2024

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 22, 2016

GeneDx

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

A variant of uncertain significance has been identified in the ALG13 gene. The N435S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The N435S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. However, this variant was not observed in approximately 5,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. -

Developmental and epileptic encephalopathy, 36

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.0030

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.20

T;.;.;.;.;T

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.48

T;T;.;T;.;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.0074

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

N;.;.;.;.;.

PhyloP100

-0.42

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.75

N;.;N;.;.;.

REVEL

Benign

0.053

Sift

Benign

0.52

T;.;T;.;.;.

Sift4G

Benign

0.11

T;T;T;T;T;T

Polyphen

0.0010

B;B;B;B;B;.

Vest4

0.039

MutPred

0.19

Loss of loop (P = 0.0374);.;.;.;.;.;

MVP

0.26

MPC

0.14

ClinPred

0.021

GERP RS

-8.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.027

gMVP

0.094

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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