chrX-111759999-A-C

Position:

chrX-111759999-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2

The NM_001099922.3(ALG13):c.3414A>C(p.Ter1138Tyrext*?) variant causes a stop lost change. The variant allele was found at a frequency of 0.00129 in 1,206,161 control chromosomes in the GnomAD database, including 2 homozygotes. There are 483 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., 20 hem., cov: 23)

Exomes 𝑓: 0.0013 ( 2 hom. 463 hem. )

Consequence

ALG13
NM_001099922.3 stop_lost

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.58

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:

ALG13 (HGNC:):

ALG13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM4

Stoplost variant in NM_001099922.3 Downstream stopcodon found after 1153 codons.

BP6

Variant X-111759999-A-C is Benign according to our data. Variant chrX-111759999-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 377466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-111759999-A-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000866 (97/112012) while in subpopulation NFE AF= 0.00152 (81/53243). AF 95% confidence interval is 0.00125. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 20 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG13	NM_001099922.3 linkuse as main transcript	c.3414A>C	p.Ter1138Tyrext*?	stop_lost	27/27	ENST00000394780.8	NP_001093392.1	Q9NP73-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG13	ENST00000394780.8 linkuse as main transcript	c.3414A>C	p.Ter1138Tyrext*?	stop_lost	27/27	2	NM_001099922.3	ENSP00000378260.3		Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.000866

AC:

AN:

111960

Hom.:

Cov.:

AF XY:

0.000586

AC XY:

AN XY:

34112

show subpopulations

Gnomad AFR

AF:

0.000357

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000380

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000374

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00152

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000645

AC:

113

AN:

175314

Hom.:

AF XY:

0.000598

AC XY:

AN XY:

63508

show subpopulations

Gnomad AFR exome

AF:

0.000245

Gnomad AMR exome

AF:

0.000149

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000746

Gnomad SAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.0000636

Gnomad NFE exome

AF:

0.00126

Gnomad OTH exome

AF:

0.000691

GnomAD4 exome

AF:

0.00133

AC:

1457

AN:

1094149

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

463

AN XY:

359889

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.000115

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.000262

Gnomad4 FIN exome

AF:

0.000347

Gnomad4 NFE exome

AF:

0.00163

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.000866

AC:

AN:

112012

Hom.:

Cov.:

AF XY:

0.000585

AC XY:

AN XY:

34174

show subpopulations

Gnomad4 AFR

AF:

0.000356

Gnomad4 AMR

AF:

0.000380

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000375

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00152

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.000737

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00138

AC:

ESP6500AA

AF:

0.000761

AC:

ESP6500EA

AF:

0.00164

AC:

ExAC

AF:

0.000715

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2021	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Developmental and epileptic encephalopathy, 36

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2018

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 06, 2023

This variant is classified as 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

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.20

CADD

Benign

9.8

DANN

Benign

0.82

FATHMM_MKL

Pathogenic

0.98

Vest4

0.18

GERP RS

5.3

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