rs772766102

chrX-111730405-TGAA-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BS1 BS2

The NM_001099922.3(ALG13):c.2383_2385del(p.Glu795del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000907 in 1,208,532 control chromosomes in the GnomAD database, including 1 homozygotes. There are 330 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., 18 hem., cov: 23)
  • Exomes 𝑓: 0.00094 (1 hom. 312 hem.)
• Consequence: ALG13 NM_001099922.3 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 4.48

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001099922.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant X-111730405-TGAA-T is Benign according to our data. Variant chrX-111730405-TGAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 412613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-111730405-TGAA-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000604 (68/112490) while in subpopulation NFE AF= 0.000976 (52/53284). AF 95% confidence interval is 0.000764. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 18 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG13	NM_001099922.3	c.2383_2385del	p.Glu795del	inframe_deletion	20/27	ENST00000394780.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG13	ENST00000394780.8	c.2383_2385del	p.Glu795del	inframe_deletion	20/27	2	NM_001099922.3	A2

Frequencies

GnomAD3 genomes AF: 0.000604 AC: 68 AN: 112490 Hom.: 0 Cov.: 23 AF XY: 0.000519 AC XY: 18 AN XY: 34654

Gnomad AFR AF: 0.0000322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000283

Gnomad ASJ AF: 0.00377

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000976

Gnomad OTH AF: 0.00131

GnomAD3 exomes AF: 0.000439 AC: 78 AN: 177526 Hom.: 0 AF XY: 0.000366 AC XY: 24 AN XY: 65508

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000735

Gnomad ASJ exome AF: 0.00324

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000126

Gnomad NFE exome AF: 0.000613

Gnomad OTH exome AF: 0.000454

GnomAD4 exome AF: 0.000938 AC: 1028 AN: 1096042 Hom.: 1 AF XY: 0.000863 AC XY: 312 AN XY: 361688

Gnomad4 AFR exome AF: 0.000152

Gnomad4 AMR exome AF: 0.0000854

Gnomad4 ASJ exome AF: 0.00393

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000148

Gnomad4 NFE exome AF: 0.00107

Gnomad4 OTH exome AF: 0.000783

GnomAD4 genome AF: 0.000604 AC: 68 AN: 112490 Hom.: 0 Cov.: 23 AF XY: 0.000519 AC XY: 18 AN XY: 34654

Gnomad4 AFR AF: 0.0000322

Gnomad4 AMR AF: 0.000283

Gnomad4 ASJ AF: 0.00377

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000976

Gnomad4 OTH AF: 0.00131

Alfa AF: 0.00127 Hom.: 12

Bravo AF: 0.000476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:7

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jan 03, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 16, 2022	See Variant Classification Assertion Criteria. -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	ALG13: BS2 -

Developmental and epileptic encephalopathy, 36 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2017

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. -

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: rs772766102; hg19: chrX-110973633;