X-111744768-ACCTCCTCCTCCTCCTCCTCCTCCT-ACCTCCTCCTCCTCCTCCTCCTCCTCCTCCT

Position:

chrX-111744768-ACCTCCTCCTCCTCCTCCTCCTCCT-ACCTCCTCCTCCTCCTCCTCCTCCTCCTCCT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001099922.3(ALG13):c.2830_2835dupCCTCCT(p.Pro944_Pro945dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000419 in 594,036 control chromosomes in the GnomAD database, including 1 homozygotes. There are 31 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00094 ( 0 hom., 1 hem., cov: 18)

Exomes 𝑓: 0.00038 ( 1 hom. 30 hem. )

Consequence

ALG13
NM_001099922.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.159

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 -16 ACMG points.

BP6

Variant X-111744768-A-ACCTCCT is Benign according to our data. Variant chrX-111744768-A-ACCTCCT is described in ClinVar as [Likely_benign]. Clinvar id is 700610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000942 (35/37147) while in subpopulation NFE AF= 0.00136 (27/19912). AF 95% confidence interval is 0.000956. There are 0 homozygotes in gnomad4. There are 1 alleles in male gnomad4 subpopulation. Median coverage is 18. This position pass quality control queck.

BS2

High Hemizygotes in GnomAdExome4 at 30 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG13	NM_001099922.3 linkuse as main transcript	c.2830_2835dupCCTCCT	p.Pro944_Pro945dup	conservative_inframe_insertion	24/27	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.2830_2835dupCCTCCT	p.Pro944_Pro945dup	conservative_inframe_insertion	24/27	2	NM_001099922.3	ENSP00000378260.3		Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.000942

AC:

AN:

37151

Hom.:

Cov.:

AF XY:

0.000140

AC XY:

AN XY:

7145

show subpopulations

Gnomad AFR

AF:

0.000503

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000797

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0110

Gnomad NFE

AF:

0.00136

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000692

AC:

AN:

33243

Hom.:

AF XY:

0.000176

AC XY:

AN XY:

5669

show subpopulations

Gnomad AFR exome

AF:

0.000714

Gnomad AMR exome

AF:

0.000957

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000384

AC:

214

AN:

556889

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

158355

show subpopulations

Gnomad4 AFR exome

AF:

0.000346

Gnomad4 AMR exome

AF:

0.000727

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000325

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.0000538

Gnomad4 NFE exome

AF:

0.000404

Gnomad4 OTH exome

AF:

0.000369

GnomAD4 genome

AF:

0.000942

AC:

AN:

37147

Hom.:

Cov.:

AF XY:

0.000140

AC XY:

AN XY:

7145

show subpopulations

Gnomad4 AFR

AF:

0.000503

Gnomad4 AMR

AF:

0.000794

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00136

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 27, 2024

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. -

Developmental and epileptic encephalopathy, 36

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 21, 2024

- -

ALG13-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 08, 2021

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). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

ALG13: BP3 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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