rs3027818

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.3058A>G(p.Thr1020Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,207,107 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 190 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 Benign (★★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 9 hem., cov: 22)

Exomes 𝑓: 0.00028 ( 0 hom. 181 hem. )

Consequence

ALG13
NM_001099922.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.698

Publications

0 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=0.0034748316).

BP6

Variant X-111757672-A-G is Benign according to our data. Variant chrX-111757672-A-G is described in ClinVar as [Benign]. Clinvar id is 412612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000108 (12/111041) while in subpopulation SAS AF = 0.00348 (9/2589). AF 95% confidence interval is 0.00181. There are 0 homozygotes in GnomAd4. There are 9 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG13	NM_001099922.3 link	c.3058A>G	p.Thr1020Ala	missense_variant	Exon 26 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.3058A>G	p.Thr1020Ala	missense_variant	Exon 26 of 27	2	NM_001099922.3	ENSP00000378260.3		Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.000108

AC:

AN:

110991

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000759

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00347

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000673

GnomAD2 exomes

AF:

0.000595

AC:

106

AN:

178107

AF XY:

0.000908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000405

Gnomad EAS exome

AF:

0.0000744

Gnomad FIN exome

AF:

0.0000629

Gnomad NFE exome

AF:

0.0000127

Gnomad OTH exome

AF:

0.000680

GnomAD4 exome

AF:

0.000282

AC:

309

AN:

1096066

Hom.:

Cov.:

AF XY:

0.000501

AC XY:

181

AN XY:

361630

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26346

American (AMR)

AF:

0.00

AC:

AN:

35141

Ashkenazi Jewish (ASJ)

AF:

0.000310

AC:

AN:

19370

East Asian (EAS)

AF:

0.0000332

AC:

AN:

30157

South Asian (SAS)

AF:

0.00485

AC:

262

AN:

54055

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40510

Middle Eastern (MID)

AF:

0.000728

AC:

AN:

4121

European-Non Finnish (NFE)

AF:

0.0000143

AC:

AN:

840354

Other (OTH)

AF:

0.000543

AC:

AN:

46012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000108

AC:

AN:

111041

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

AN XY:

33235

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30604

American (AMR)

AF:

0.00

AC:

AN:

10314

Ashkenazi Jewish (ASJ)

AF:

0.000759

AC:

AN:

2634

East Asian (EAS)

AF:

0.00

AC:

AN:

3524

South Asian (SAS)

AF:

0.00348

AC:

AN:

2589

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5974

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52996

Other (OTH)

AF:

0.000665

AC:

AN:

1503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000507

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.000747

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 36

Benign:2

Nov 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jul 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.21

T;.;.;.;.

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.49

T;T;.;T;.

M_CAP

Benign

0.0047

MetaRNN

Benign

0.0035

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.95

L;.;.;.;.

PhyloP100

-0.70

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.98

N;.;N;.;.

REVEL

Benign

0.023

Sift

Benign

0.34

T;.;T;.;.

Sift4G

Benign

0.50

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.049

MutPred

0.42

Loss of glycosylation at T1020 (P = 0.004);.;.;.;.;

MVP

0.15

MPC

0.17

ClinPred

0.0072

GERP RS

-4.1

Varity_R

0.050

gMVP

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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rs3027818

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