chrX-111744768-ACCT-A

Position:

• chrX-111744768-ACCT-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001099922.3(ALG13):​c.2833_2835delCCT​(p.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 0.0483 in 455,685 control chromosomes in the GnomAD database, including 65 homozygotes. There are 1,205 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (35 hom., 64 hem., cov: 9)
  • Exomes 𝑓: 0.049 (30 hom. 1141 hem.)
• Consequence: ALG13 NM_001099922.3 conservative_inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.159

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant X-111744768-ACCT-A is Benign according to our data. Variant chrX-111744768-ACCT-A is described in ClinVar as [Benign]. Clinvar id is 238295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-111744768-ACCT-A is described in Lovd as [Benign]. Variant chrX-111744768-ACCT-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG13	NM_001099922.3	c.2833_2835delCCT	p.Pro945del	conservative_inframe_deletion	24/27	ENST00000394780.8	NP_001093392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG13	ENST00000394780.8	c.2833_2835delCCT	p.Pro945del	conservative_inframe_deletion	24/27	2	NM_001099922.3	ENSP00000378260.3

Frequencies

GnomAD3 genomes AF: 0.0378 AC: 1398 AN: 37019 Hom.: 35 Cov.: 9 AF XY: 0.00898 AC XY: 64 AN XY: 7127

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.0299

Gnomad EAS AF: 0.00995

Gnomad SAS AF: 0.0167

Gnomad FIN AF: 0.00338

Gnomad MID AF: 0.0330

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0447

GnomAD3 exomes AF: 0.0951 AC: 3160 AN: 33243 Hom.: 4 AF XY: 0.0120 AC XY: 68 AN XY: 5669

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.132

Gnomad SAS exome AF: 0.0903

Gnomad FIN exome AF: 0.0548

Gnomad NFE exome AF: 0.0709

Gnomad OTH exome AF: 0.0941

GnomAD4 exome AF: 0.0493 AC: 20634 AN: 418670 Hom.: 30 AF XY: 0.0109 AC XY: 1141 AN XY: 104424

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.0731

Gnomad4 ASJ exome AF: 0.0837

Gnomad4 EAS exome AF: 0.0619

Gnomad4 SAS exome AF: 0.0550

Gnomad4 FIN exome AF: 0.0309

Gnomad4 NFE exome AF: 0.0444

Gnomad4 OTH exome AF: 0.0589

GnomAD4 genome AF: 0.0377 AC: 1397 AN: 37015 Hom.: 35 Cov.: 9 AF XY: 0.00898 AC XY: 64 AN XY: 7127

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0204

Gnomad4 ASJ AF: 0.0299

Gnomad4 EAS AF: 0.00995

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.00338

Gnomad4 NFE AF: 0.0133

Gnomad4 OTH AF: 0.0466

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 06, 2019	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 21, 2019	- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2022

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. -

Developmental and epileptic encephalopathy, 36 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

ALG13-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 05, 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). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs56717389; hg19: chrX-110987996;