rs146925326

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001099922.3(ALG13):c.183C>T(p.Tyr61Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,197,624 control chromosomes in the GnomAD database, including 139 homozygotes. There are 5,188 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 12 hom., 281 hem., cov: 23)

Exomes 𝑓: 0.015 ( 127 hom. 4907 hem. )

Consequence

ALG13
NM_001099922.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.657

Publications

5 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039321184).

BP6

Variant X-111682233-C-T is Benign according to our data. Variant chrX-111682233-C-T is described in ClinVar as Benign. ClinVar VariationId is 238290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.657 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00923 (1035/112115) while in subpopulation NFE AF = 0.0165 (877/53223). AF 95% confidence interval is 0.0156. There are 12 homozygotes in GnomAd4. There are 281 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG13	NM_001099922.3 link	c.183C>T	p.Tyr61Tyr	synonymous_variant	Exon 2 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.183C>T	p.Tyr61Tyr	synonymous_variant	Exon 2 of 27	2	NM_001099922.3	ENSP00000378260.3		Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.00925

AC:

1036

AN:

112060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00198

Gnomad ASJ

AF:

0.00264

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00114

Gnomad FIN

AF:

0.00850

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0165

Gnomad OTH

AF:

0.00397

GnomAD2 exomes

AF:

0.00809

AC:

1393

AN:

172113

AF XY:

0.00763

show subpopulations

Gnomad AFR exome

AF:

0.00207

Gnomad AMR exome

AF:

0.00305

Gnomad ASJ exome

AF:

0.000990

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00824

Gnomad NFE exome

AF:

0.0142

Gnomad OTH exome

AF:

0.00555

GnomAD4 exome

AF:

0.0146

AC:

15858

AN:

1085509

Hom.:

127

Cov.:

AF XY:

0.0139

AC XY:

4907

AN XY:

352453

show subpopulations

African (AFR)

AF:

0.00196

AC:

AN:

26031

American (AMR)

AF:

0.00311

AC:

106

AN:

34113

Ashkenazi Jewish (ASJ)

AF:

0.00199

AC:

AN:

19057

East Asian (EAS)

AF:

0.00

AC:

AN:

29699

South Asian (SAS)

AF:

0.00129

AC:

AN:

51758

European-Finnish (FIN)

AF:

0.00892

AC:

359

AN:

40267

Middle Eastern (MID)

AF:

0.000490

AC:

AN:

4078

European-Non Finnish (NFE)

AF:

0.0176

AC:

14677

AN:

834956

Other (OTH)

AF:

0.0123

AC:

558

AN:

45550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

495

990

1485

1980

2475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.00923

AC:

1035

AN:

112115

Hom.:

Cov.:

AF XY:

0.00819

AC XY:

281

AN XY:

34293

show subpopulations

African (AFR)

AF:

0.00223

AC:

AN:

30873

American (AMR)

AF:

0.00198

AC:

AN:

10618

Ashkenazi Jewish (ASJ)

AF:

0.00264

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3565

South Asian (SAS)

AF:

0.00114

AC:

AN:

2635

European-Finnish (FIN)

AF:

0.00850

AC:

AN:

6120

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0165

AC:

877

AN:

53223

Other (OTH)

AF:

0.00392

AC:

AN:

1530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

124

165

206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00719

Hom.:

Bravo

AF:

0.00844

TwinsUK

AF:

0.0208

AC:

ALSPAC

AF:

0.0145

AC:

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.0162

AC:

109

ExAC

AF:

0.00893

AC:

1084

ClinVar

Significance: Benign

Submissions summary: Benign:6

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 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 19, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jan 14, 2016

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. -

Inborn genetic diseases

Benign:1

Apr 14, 2016

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

Uncertain

0.42

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.52

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0039

PhyloP100

0.66

Sift4G

Pathogenic

0.0010

Polyphen

0.082

Vest4

0.049

MVP

0.49

GERP RS

4.3

PromoterAI

-0.015

Neutral

(source)

Mutation Taster

=288/12

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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