rs142841538

Positions:

chrX-111736801-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001099922.3(ALG13):c.2617G>C(p.Ala873Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,208,505 control chromosomes in the GnomAD database, including 3 homozygotes. There are 825 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., 68 hem., cov: 23)

Exomes 𝑓: 0.0022 ( 3 hom. 757 hem. )

Consequence

ALG13
NM_001099922.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.243

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002595842).

BP6

Variant X-111736801-G-C is Benign according to our data. Variant chrX-111736801-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 412610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-111736801-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00164 (183/111615) while in subpopulation NFE AF= 0.00199 (106/53176). AF 95% confidence interval is 0.00169. There are 0 homozygotes in gnomad4. There are 68 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 68 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG13	NM_001099922.3 linkuse as main transcript	c.2617G>C	p.Ala873Pro	missense_variant	23/27	ENST00000394780.8	NP_001093392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG13	ENST00000394780.8 linkuse as main transcript	c.2617G>C	p.Ala873Pro	missense_variant	23/27	2	NM_001099922.3	ENSP00000378260	A2	Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.00164

AC:

183

AN:

111562

Hom.:

Cov.:

AF XY:

0.00202

AC XY:

AN XY:

33742

show subpopulations

Gnomad AFR

AF:

0.000261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000668

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000375

Gnomad FIN

AF:

0.0100

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00199

Gnomad OTH

AF:

0.000669

GnomAD3 exomes

AF:

0.00207

AC:

370

AN:

178475

Hom.:

AF XY:

0.00213

AC XY:

141

AN XY:

66269

show subpopulations

Gnomad AFR exome

AF:

0.000325

Gnomad AMR exome

AF:

0.000772

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000263

Gnomad FIN exome

AF:

0.0106

Gnomad NFE exome

AF:

0.00207

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00216

AC:

2370

AN:

1096890

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

757

AN XY:

362410

show subpopulations

Gnomad4 AFR exome

AF:

0.000227

Gnomad4 AMR exome

AF:

0.000825

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000203

Gnomad4 FIN exome

AF:

0.00940

Gnomad4 NFE exome

AF:

0.00219

Gnomad4 OTH exome

AF:

0.00226

GnomAD4 genome

AF:

0.00164

AC:

183

AN:

111615

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

AN XY:

33805

show subpopulations

Gnomad4 AFR

AF:

0.000260

Gnomad4 AMR

AF:

0.000667

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000377

Gnomad4 FIN

AF:

0.0100

Gnomad4 NFE

AF:

0.00199

Gnomad4 OTH

AF:

0.000661

Alfa

AF:

0.00184

Hom.:

Bravo

AF:

0.00102

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00173

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00127

AC:

ExAC

AF:

0.00222

AC:

267

EpiCase

AF:

0.00181

EpiControl

AF:

0.00173

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 08, 2019	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Developmental and epileptic encephalopathy, 36

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 09, 2017

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

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2017

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. -

ALG13-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.6

DANN

Benign

0.92

DEOGEN2

Benign

0.36

T;.;.;.;.

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.58

T;T;.;T;.

MetaRNN

Benign

0.0026

T;T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.5

L;.;.;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.70

N;.;N;.;.

REVEL

Benign

0.056

Sift

Benign

0.062

T;.;T;.;.

Sift4G

Benign

0.21

T;T;D;D;D

Polyphen

0.0040

B;B;D;D;D

Vest4

0.077

MVP

0.56

MPC

0.44

ClinPred

0.0041

GERP RS

-0.63

Varity_R

0.080

gMVP

0.34

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