rs200066623

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001099922.3(ALG13):c.2672C>T(p.Ser891Phe) variant causes a missense change. The variant allele was found at a frequency of 0.003 in 1,206,632 control chromosomes in the GnomAD database, including 25 homozygotes. There are 1,256 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., 183 hem., cov: 23)

Exomes 𝑓: 0.0029 ( 24 hom. 1073 hem. )

Consequence

ALG13
NM_001099922.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 5.25

Publications

2 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038899481).

BP6

Variant X-111736856-C-T is Benign according to our data. Variant chrX-111736856-C-T is described in ClinVar as Benign. ClinVar VariationId is 238293.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 = 0.00364 (408/112016) while in subpopulation NFE AF = 0.003 (160/53277). AF 95% confidence interval is 0.00262. There are 1 homozygotes in GnomAd4. There are 183 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 183 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG13	NM_001099922.3 link	c.2672C>T	p.Ser891Phe	missense_variant	Exon 23 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.2672C>T	p.Ser891Phe	missense_variant	Exon 23 of 27	2	NM_001099922.3	ENSP00000378260.3		Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.00364

AC:

408

AN:

111964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000974

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000380

Gnomad ASJ

AF:

0.00679

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0363

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00300

Gnomad OTH

AF:

0.00265

GnomAD2 exomes

AF:

0.00512

AC:

888

AN:

173528

AF XY:

0.00525

show subpopulations

Gnomad AFR exome

AF:

0.000249

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.00677

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0386

Gnomad NFE exome

AF:

0.00224

Gnomad OTH exome

AF:

0.00468

GnomAD4 exome

AF:

0.00294

AC:

3215

AN:

1094616

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

1073

AN XY:

360300

show subpopulations

African (AFR)

AF:

0.000343

AC:

AN:

26263

American (AMR)

AF:

0.00109

AC:

AN:

34821

Ashkenazi Jewish (ASJ)

AF:

0.00696

AC:

134

AN:

19262

East Asian (EAS)

AF:

0.00

AC:

AN:

30033

South Asian (SAS)

AF:

0.0000375

AC:

AN:

53266

European-Finnish (FIN)

AF:

0.0366

AC:

1480

AN:

40463

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

4122

European-Non Finnish (NFE)

AF:

0.00165

AC:

1389

AN:

840444

Other (OTH)

AF:

0.00344

AC:

158

AN:

45942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

116

232

348

464

580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.00364

AC:

408

AN:

112016

Hom.:

Cov.:

AF XY:

0.00535

AC XY:

183

AN XY:

34186

show subpopulations

African (AFR)

AF:

0.0000972

AC:

AN:

30866

American (AMR)

AF:

0.000380

AC:

AN:

10537

Ashkenazi Jewish (ASJ)

AF:

0.00679

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3550

South Asian (SAS)

AF:

0.00

AC:

AN:

2672

European-Finnish (FIN)

AF:

0.0363

AC:

219

AN:

6028

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00300

AC:

160

AN:

53277

Other (OTH)

AF:

0.00261

AC:

AN:

1531

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.00229

Hom.:

110

Bravo

AF:

0.00108

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.000381

AC:

ESP6500EA

AF:

0.00127

AC:

ExAC

AF:

0.00406

AC:

489

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:2

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 11, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

May 09, 2017

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

D;.;.;.;.

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.80

T;T;.;T;.

MetaRNN

Benign

0.0039

T;T;T;T;T

MetaSVM

Uncertain

-0.069

MutationAssessor

Benign

1.9

L;.;.;.;.

PhyloP100

5.3

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.6

D;.;N;.;.

REVEL

Benign

0.15

Sift

Uncertain

0.0050

D;.;D;.;.

Sift4G

Uncertain

0.0070

D;D;D;D;D

Polyphen

0.98

D;D;P;P;P

Vest4

0.26

MVP

0.67

MPC

0.56

ClinPred

0.030

GERP RS

5.5

Varity_R

0.63

gMVP

0.24

Mutation Taster

=91/9

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