rs201055779

Positions:

chrX-111757622-A-G

Variant summary

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

The NM_001099922.3(ALG13):c.3008A>G(p.Tyr1003Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000813 in 1,204,885 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 31 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., 7 hem., cov: 22)

Exomes 𝑓: 0.000068 ( 0 hom. 24 hem. )

Consequence

ALG13
NM_001099922.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.785

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=0.01303643).

BP6

Variant X-111757622-A-G is Benign according to our data. Variant chrX-111757622-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 390901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000211 (23/109178) while in subpopulation EAS AF= 0.00145 (5/3454). AF 95% confidence interval is 0.00057. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG13	NM_001099922.3 linkuse as main transcript	c.3008A>G	p.Tyr1003Cys	missense_variant	26/27	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.3008A>G	p.Tyr1003Cys	missense_variant	26/27	2	NM_001099922.3	ENSP00000378260	A2	Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.000211

AC:

AN:

109131

Hom.:

Cov.:

AF XY:

0.000222

AC XY:

AN XY:

31553

show subpopulations

Gnomad AFR

AF:

0.000502

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000100

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00144

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000380

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000154

AC:

AN:

175055

Hom.:

AF XY:

0.000127

AC XY:

AN XY:

63157

show subpopulations

Gnomad AFR exome

AF:

0.000413

Gnomad AMR exome

AF:

0.0000374

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00129

Gnomad SAS exome

AF:

0.0000549

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000259

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.0000684

AC:

AN:

1095707

Hom.:

Cov.:

AF XY:

0.0000664

AC XY:

AN XY:

361369

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.0000571

Gnomad4 ASJ exome

AF:

0.0000518

Gnomad4 EAS exome

AF:

0.000465

Gnomad4 SAS exome

AF:

0.0000372

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000202

Gnomad4 OTH exome

AF:

0.000739

GnomAD4 genome

AF:

0.000211

AC:

AN:

109178

Hom.:

Cov.:

AF XY:

0.000221

AC XY:

AN XY:

31610

show subpopulations

Gnomad4 AFR

AF:

0.000501

Gnomad4 AMR

AF:

0.0000999

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00145

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000380

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000343

Hom.:

Bravo

AF:

0.000249

ESP6500AA

AF:

0.000761

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000166

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 36

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2019	In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2019	- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2018

This alteration is classified as likely 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

Dec 13, 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

0.052

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.45

CADD

Benign

7.2

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.77

D;.;.;.;.

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.69

T;T;.;T;.

M_CAP

Benign

0.027

MetaRNN

Benign

0.013

T;T;T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.7

L;.;.;.;.

MutationTaster

Benign

0.74

N;N

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-5.0

D;.;D;.;.

REVEL

Benign

0.087

Sift

Uncertain

0.0020

D;.;D;.;.

Sift4G

Uncertain

0.030

D;D;D;D;D

Polyphen

0.0030

B;D;D;D;D

Vest4

0.26

MVP

0.26

MPC

0.22

ClinPred

0.057

GERP RS

-0.25

Varity_R

0.39

gMVP

0.22

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