X-111736856-C-T

Position:

chrX-111736856-C-T

Variant summary

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

The NM_001099922.3(ALG13):c.2672C>T(p.Ser891Phe) variant causes a missense change. The variant allele was found at a frequency of 0.003 in 1,206,632 control chromosomes in the GnomAD database, including 25 homozygotes. There are 1,256 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., 183 hem., cov: 23)

Exomes 𝑓: 0.0029 ( 24 hom. 1073 hem. )

Consequence

ALG13
NM_001099922.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 5.25

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038899481).

BP6

Variant X-111736856-C-T is Benign according to our data. Variant chrX-111736856-C-T is described in ClinVar as [Benign]. Clinvar id is 238293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-111736856-C-T is described in Lovd as [Likely_benign]. Variant chrX-111736856-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00364 (408/112016) while in subpopulation NFE AF= 0.003 (160/53277). AF 95% confidence interval is 0.00262. There are 1 homozygotes in gnomad4. There are 183 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 183 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG13	NM_001099922.3 linkuse as main transcript	c.2672C>T	p.Ser891Phe	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.2672C>T	p.Ser891Phe	missense_variant	23/27	2	NM_001099922.3	ENSP00000378260	A2	Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.00364

AC:

408

AN:

111964

Hom.:

Cov.:

AF XY:

0.00536

AC XY:

183

AN XY:

34124

show subpopulations

Gnomad AFR

AF:

0.0000974

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000380

Gnomad ASJ

AF:

0.00679

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0363

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00300

Gnomad OTH

AF:

0.00265

GnomAD3 exomes

AF:

0.00512

AC:

888

AN:

173528

Hom.:

AF XY:

0.00525

AC XY:

323

AN XY:

61564

show subpopulations

Gnomad AFR exome

AF:

0.000249

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.00677

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0386

Gnomad NFE exome

AF:

0.00224

Gnomad OTH exome

AF:

0.00468

GnomAD4 exome

AF:

0.00294

AC:

3215

AN:

1094616

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

1073

AN XY:

360300

show subpopulations

Gnomad4 AFR exome

AF:

0.000343

Gnomad4 AMR exome

AF:

0.00109

Gnomad4 ASJ exome

AF:

0.00696

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000375

Gnomad4 FIN exome

AF:

0.0366

Gnomad4 NFE exome

AF:

0.00165

Gnomad4 OTH exome

AF:

0.00344

GnomAD4 genome

AF:

0.00364

AC:

408

AN:

112016

Hom.:

Cov.:

AF XY:

0.00535

AC XY:

183

AN XY:

34186

show subpopulations

Gnomad4 AFR

AF:

0.0000972

Gnomad4 AMR

AF:

0.000380

Gnomad4 ASJ

AF:

0.00679

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0363

Gnomad4 NFE

AF:

0.00300

Gnomad4 OTH

AF:

0.00261

Alfa

AF:

0.00245

Hom.:

110

Bravo

AF:

0.00108

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.000381

AC:

ESP6500EA

AF:

0.00127

AC:

ExAC

AF:

0.00406

AC:

489

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 11, 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. -
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	Jan 25, 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 09, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

D;.;.;.;.

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.80

T;T;.;T;.

MetaRNN

Benign

0.0039

T;T;T;T;T

MetaSVM

Uncertain

-0.069

MutationAssessor

Benign

1.9

L;.;.;.;.

MutationTaster

Benign

0.96

D;N

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.6

D;.;N;.;.

REVEL

Benign

0.15

Sift

Uncertain

0.0050

D;.;D;.;.

Sift4G

Uncertain

0.0070

D;D;D;D;D

Polyphen

0.98

D;D;P;P;P

Vest4

0.26

MVP

0.67

MPC

0.56

ClinPred

0.030

GERP RS

5.5

Varity_R

0.63

gMVP

0.24

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