rs370438099

Positions:

chrX-111728181-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001099922.3(ALG13):c.2248-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,209,347 control chromosomes in the GnomAD database, including 30 homozygotes. There are 1,691 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 14 hom., 111 hem., cov: 23)

Exomes 𝑓: 0.0037 ( 16 hom. 1580 hem. )

Consequence

ALG13
NM_001099922.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.004647

Clinical Significance

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

Conservation

PhyloP100: 0.0570

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant X-111728181-A-G is Benign according to our data. Variant chrX-111728181-A-G is described in ClinVar as [Benign]. Clinvar id is 380781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-111728181-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00362 (404/111747) while in subpopulation SAS AF= 0.0154 (41/2670). AF 95% confidence interval is 0.0116. There are 14 homozygotes in gnomad4. There are 111 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG13	NM_001099922.3 linkuse as main transcript	c.2248-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		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.2248-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_001099922.3	ENSP00000378260	A2	Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.00362

AC:

404

AN:

111692

Hom.:

Cov.:

AF XY:

0.00328

AC XY:

111

AN XY:

33866

show subpopulations

Gnomad AFR

AF:

0.000521

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.000762

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.000995

Gnomad MID

AF:

0.00837

Gnomad NFE

AF:

0.00369

Gnomad OTH

AF:

0.00267

GnomAD3 exomes

AF:

0.00397

AC:

710

AN:

178742

Hom.:

AF XY:

0.00496

AC XY:

330

AN XY:

66546

show subpopulations

Gnomad AFR exome

AF:

0.000324

Gnomad AMR exome

AF:

0.000658

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0196

Gnomad FIN exome

AF:

0.00113

Gnomad NFE exome

AF:

0.00360

Gnomad OTH exome

AF:

0.00338

GnomAD4 exome

AF:

0.00366

AC:

4019

AN:

1097600

Hom.:

Cov.:

AF XY:

0.00435

AC XY:

1580

AN XY:

363120

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.000739

Gnomad4 ASJ exome

AF:

0.000103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0188

Gnomad4 FIN exome

AF:

0.00190

Gnomad4 NFE exome

AF:

0.00324

Gnomad4 OTH exome

AF:

0.00310

GnomAD4 genome

AF:

0.00362

AC:

404

AN:

111747

Hom.:

Cov.:

AF XY:

0.00327

AC XY:

111

AN XY:

33931

show subpopulations

Gnomad4 AFR

AF:

0.000520

Gnomad4 AMR

AF:

0.000761

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0154

Gnomad4 FIN

AF:

0.000995

Gnomad4 NFE

AF:

0.00369

Gnomad4 OTH

AF:

0.00263

Alfa

AF:

0.00273

Hom.:

Bravo

AF:

0.00348

EpiCase

AF:

0.00474

EpiControl

AF:

0.00518

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 36

Benign:3

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	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Oct 04, 2021	- -

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	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 15, 2016

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

Sep 25, 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

BayesDel_noAF

Benign

-0.40

CADD

Benign

2.7

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0046

dbscSNV1_RF

Benign

0.16

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