rs112837367

chrX-111723888-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001099922.3(ALG13):c.1591T>C(p.Leu531=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 1,141,864 control chromosomes in the GnomAD database, including 1 homozygotes. There are 60 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00085 (0 hom., 23 hem., cov: 23)
  • Exomes 𝑓: 0.00013 (1 hom. 37 hem.)
• Consequence: ALG13 NM_001099922.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.650

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant X-111723888-T-C is Benign according to our data. Variant chrX-111723888-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 387963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.65 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000848 (95/111992) while in subpopulation AFR AF= 0.00275 (85/30896). AF 95% confidence interval is 0.00228. There are 0 homozygotes in gnomad4. There are 23 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 23 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG13	NM_001099922.3	c.1591T>C	p.Leu531=	synonymous_variant	14/27	ENST00000394780.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG13	ENST00000394780.8	c.1591T>C	p.Leu531=	synonymous_variant	14/27	2	NM_001099922.3	A2

Frequencies

GnomAD3 genomes AF: 0.000849 AC: 95 AN: 111937 Hom.: 0 Cov.: 23 AF XY: 0.000675 AC XY: 23 AN XY: 34081

Gnomad AFR AF: 0.00276

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000570

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00844

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.000670

GnomAD3 exomes AF: 0.000350 AC: 44 AN: 125641 Hom.: 0 AF XY: 0.000333 AC XY: 10 AN XY: 30015

Gnomad AFR exome AF: 0.00328

Gnomad AMR exome AF: 0.000642

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000105

Gnomad SAS exome AF: 0.0000866

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000320

GnomAD4 exome AF: 0.000134 AC: 138 AN: 1029872 Hom.: 1 Cov.: 20 AF XY: 0.000120 AC XY: 37 AN XY: 309488

Gnomad4 AFR exome AF: 0.00286

Gnomad4 AMR exome AF: 0.000657

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000347

Gnomad4 SAS exome AF: 0.000194

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000288

Gnomad4 OTH exome AF: 0.000390

GnomAD4 genome AF: 0.000848 AC: 95 AN: 111992 Hom.: 0 Cov.: 23 AF XY: 0.000674 AC XY: 23 AN XY: 34146

Gnomad4 AFR AF: 0.00275

Gnomad4 AMR AF: 0.000569

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.000661

Alfa AF: 0.000783 Hom.: 2

Bravo AF: 0.00128

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 36 Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Sep 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jun 23, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2016

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	0.096
Dann	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs112837367; hg19: chrX-110967116;