Genetic Variant ALG13:p.Pro942_Pro945del (chrX-111744768-ACCTCCTCCTCCT-A) – ACMG Classification: Benign (-16 pts)

Variant summary

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

The NM_001099922.3(ALG13):c.2824_2835delCCTCCTCCTCCT(p.Pro942_Pro945del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000456 in 594,412 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 82 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., 4 hem., cov: 9)

Exomes 𝑓: 0.00043 ( 0 hom. 78 hem. )

Consequence

ALG13
NM_001099922.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.322

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 -16 ACMG points.

BP6

Variant X-111744768-ACCTCCTCCTCCT-A is Benign according to our data. Variant chrX-111744768-ACCTCCTCCTCCT-A is described in ClinVar as [Likely_benign]. Clinvar id is 516988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000861 (32/37156) while in subpopulation AMR AF= 0.00278 (7/2520). AF 95% confidence interval is 0.0013. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 9. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG13	NM_001099922.3 link	c.2824_2835delCCTCCTCCTCCT	p.Pro942_Pro945del	conservative_inframe_deletion	Exon 24 of 27	ENST00000394780.8	NP_001093392.1	Q9NP73-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG13	ENST00000394780.8 link	c.2824_2835delCCTCCTCCTCCT	p.Pro942_Pro945del	conservative_inframe_deletion	Exon 24 of 27	2	NM_001099922.3	ENSP00000378260.3		Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.000861

AC:

AN:

37160

Hom.:

Cov.:

AF XY:

0.000560

AC XY:

AN XY:

7144

show subpopulations

Gnomad AFR

AF:

0.000101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00279

Gnomad ASJ

AF:

0.00599

Gnomad EAS

AF:

0.00248

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000825

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000703

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000993

AC:

AN:

33243

Hom.:

AF XY:

0.00106

AC XY:

AN XY:

5669

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000957

Gnomad ASJ exome

AF:

0.00451

Gnomad EAS exome

AF:

0.000758

Gnomad SAS exome

AF:

0.00241

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000762

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000429

AC:

239

AN:

557256

Hom.:

AF XY:

0.000492

AC XY:

AN XY:

158534

show subpopulations

Gnomad4 AFR exome

AF:

0.0000692

Gnomad4 AMR exome

AF:

0.000545

Gnomad4 ASJ exome

AF:

0.00347

Gnomad4 EAS exome

AF:

0.00104

Gnomad4 SAS exome

AF:

0.000678

Gnomad4 FIN exome

AF:

0.000377

Gnomad4 NFE exome

AF:

0.000323

Gnomad4 OTH exome

AF:

0.000697

GnomAD4 genome

AF:

0.000861

AC:

AN:

37156

Hom.:

Cov.:

AF XY:

0.000560

AC XY:

AN XY:

7144

show subpopulations

Gnomad4 AFR

AF:

0.000101

Gnomad4 AMR

AF:

0.00278

Gnomad4 ASJ

AF:

0.00599

Gnomad4 EAS

AF:

0.00248

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000825

Gnomad4 NFE

AF:

0.000703

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 36

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ALG13-related disorder

Benign:1

Feb 23, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Mar 12, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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.

X-111744768-ACCTCCTCCTCCTCCTCCTCCTCCT-ACCTCCTCCTCCT

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