rs372521943

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4BP6BS2

The NM_001099922.3(ALG13):c.1064A>G(p.Gln355Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000249 in 1,203,755 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000027 ( 0 hom. 9 hem. )

Consequence

ALG13
NM_001099922.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.10

Publications

1 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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2679379).

BP6

Variant X-111717904-A-G is Benign according to our data. Variant chrX-111717904-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286496. Variant chrX-111717904-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286496. Variant chrX-111717904-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286496. Variant chrX-111717904-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286496. Variant chrX-111717904-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286496. Variant chrX-111717904-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286496. Variant chrX-111717904-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286496. Variant chrX-111717904-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286496. Variant chrX-111717904-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286496. Variant chrX-111717904-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286496. Variant chrX-111717904-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286496. Variant chrX-111717904-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286496.

BS2

High Hemizygotes in GnomAdExome4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG13	NM_001099922.3 link	c.1064A>G	p.Gln355Arg	missense_variant	Exon 9 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.1064A>G	p.Gln355Arg	missense_variant	Exon 9 of 27	2	NM_001099922.3	ENSP00000378260.3		Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.00000898

AC:

AN:

111382

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000115

AC:

AN:

173453

AF XY:

0.0000163

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000260

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000265

AC:

AN:

1092373

Hom.:

Cov.:

AF XY:

0.0000251

AC XY:

AN XY:

358073

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26277

American (AMR)

AF:

0.00

AC:

AN:

34909

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19290

East Asian (EAS)

AF:

0.00

AC:

AN:

30159

South Asian (SAS)

AF:

0.00

AC:

AN:

53286

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40395

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4115

European-Non Finnish (NFE)

AF:

0.0000334

AC:

AN:

838040

Other (OTH)

AF:

0.0000218

AC:

AN:

45902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

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:

0.00000898

AC:

AN:

111382

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33554

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30682

American (AMR)

AF:

0.00

AC:

AN:

10398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3562

South Asian (SAS)

AF:

0.00

AC:

AN:

2654

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5912

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53106

Other (OTH)

AF:

0.00

AC:

AN:

1497

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000182

AC:

ExAC

AF:

0.0000249

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Mar 03, 2016

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy, 36

Benign:1

Aug 29, 2024

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

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;.;.;.;.;T

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.76

T;T;.;T;.;T

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.27

T;T;T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.4

M;.;.;.;.;.

PhyloP100

5.1

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.1

N;.;N;.;.;.

REVEL

Benign

0.22

Sift

Benign

0.40

T;.;T;.;.;.

Sift4G

Uncertain

0.026

D;D;T;T;T;D

Polyphen

1.0

D;D;D;D;D;.

Vest4

0.46

MVP

0.86

MPC

0.72

ClinPred

0.52

GERP RS

5.6

PromoterAI

0.032

Neutral

(source)

Varity_R

0.35

gMVP

0.29

Mutation Taster

=96/4

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over