X-111744768-ACCTCCTCCTCCTCCTCCTCCTCCT-ACCTCCTCCTCCTCCTCCTCCTCCTCCTCCT

Variant names:

• chrX-111744768-A-ACCTCCT
• rs56717389
• NM_001099922.3:c.2830_2835dupCCTCCT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• 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]

ACMG classification

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 rank	MANE	Protein	UniProt
ALG13	NM_001099922.3	c.2830_2835dupCCTCCT	p.Pro944_Pro945dup	conservative_inframe_insertion	Exon 24 of 27	ENST00000394780.8	NP_001093392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG13	ENST00000394780.8	c.2830_2835dupCCTCCT	p.Pro944_Pro945dup	conservative_inframe_insertion	Exon 24 of 27	2	NM_001099922.3	ENSP00000378260.3

Frequencies

GnomAD3 genomes AF: 0.000942 AC: 35 AN: 37151 Hom.: 0 Cov.: 18 AF XY: 0.000140 AC XY: 1 AN XY: 7145

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: 23 AN: 33243 Hom.: 1 AF XY: 0.000176 AC XY: 1 AN XY: 5669

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.: 1 Cov.: 24 AF XY: 0.000189 AC XY: 30 AN XY: 158355

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: 35 AN: 37147 Hom.: 0 Cov.: 18 AF XY: 0.000140 AC XY: 1 AN XY: 7145

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

Submissions by phenotype

Developmental and epileptic encephalopathy, 36 Benign:1

Dec 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Mar 27, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

ALG13-related disorder Benign:1

Jan 08, 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 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ALG13: BP3 -

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;