Variant X-111759989-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001099922.3(ALG13):c.3404A>G(p.Gln1135Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000464 in 1,208,105 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000049 ( 0 hom. 13 hem. )

Consequence

ALG13
NM_001099922.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.57

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07617912).

BP6

Variant X-111759989-A-G is Benign according to our data. Variant chrX-111759989-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 567269.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 13 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG13	NM_001099922.3 linkuse as main transcript	c.3404A>G	p.Gln1135Arg	missense_variant	27/27	ENST00000394780.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG13	ENST00000394780.8 linkuse as main transcript	c.3404A>G	p.Gln1135Arg	missense_variant	27/27	2	NM_001099922.3	A2	Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111651

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33847

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000113

AC:

AN:

177185

Hom.:

AF XY:

0.00

AC XY:

AN XY:

65207

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000256

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000492

AC:

AN:

1096454

Hom.:

Cov.:

AF XY:

0.0000359

AC XY:

AN XY:

362056

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000583

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111651

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33847

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000831

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 36

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.38

T;.;.;.;.

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.39

T;T;.;T;.

M_CAP

Benign

0.025

MetaRNN

Benign

0.076

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.7

L;.;.;.;.

MutationTaster

Benign

0.95

N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.0

N;.;N;.;.

REVEL

Benign

0.030

Sift

Pathogenic

0.0

D;.;D;.;.

Sift4G

Uncertain

0.0020

D;D;D;D;D

Polyphen

0.028

B;B;B;B;B

Vest4

0.090

MVP

0.60

MPC

0.19

ClinPred

0.14

GERP RS

1.4

Varity_R

0.36

gMVP

0.28

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over