rs5985637

Positions:

• chrX-111720110-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.1266T>C​(p.Gly422=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,188,699 control chromosomes in the GnomAD database, including 162 homozygotes. There are 5,887 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (32 hom., 411 hem., cov: 23)
  • Exomes 𝑓: 0.017 (130 hom. 5476 hem.)
• Consequence: ALG13 NM_001099922.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.78

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=-0.72).
• BP6: Variant X-111720110-T-C is Benign according to our data. Variant chrX-111720110-T-C is described in ClinVar as [Benign]. Clinvar id is 238289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-111720110-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.78 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0135 (1516/112035) while in subpopulation AMR AF= 0.0239 (254/10608). AF 95% confidence interval is 0.0215. There are 32 homozygotes in gnomad4. There are 411 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 32 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG13	NM_001099922.3	c.1266T>C	p.Gly422=	synonymous_variant	11/27	ENST00000394780.8	NP_001093392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG13	ENST00000394780.8	c.1266T>C	p.Gly422=	synonymous_variant	11/27	2	NM_001099922.3	ENSP00000378260	A2

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 1515 AN: 111980 Hom.: 32 Cov.: 23 AF XY: 0.0120 AC XY: 410 AN XY: 34150

Gnomad AFR AF: 0.00221

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.00908

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00148

Gnomad FIN AF: 0.00347

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0146

GnomAD3 exomes AF: 0.0110 AC: 1680 AN: 152142 Hom.: 7 AF XY: 0.00957 AC XY: 431 AN XY: 45028

Gnomad AFR exome AF: 0.00217

Gnomad AMR exome AF: 0.0130

Gnomad ASJ exome AF: 0.0151

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00280

Gnomad FIN exome AF: 0.00305

Gnomad NFE exome AF: 0.0169

Gnomad OTH exome AF: 0.0120

GnomAD4 exome AF: 0.0170 AC: 18322 AN: 1076664 Hom.: 130 Cov.: 25 AF XY: 0.0158 AC XY: 5476 AN XY: 346094

Gnomad4 AFR exome AF: 0.00232

Gnomad4 AMR exome AF: 0.0138

Gnomad4 ASJ exome AF: 0.0154

Gnomad4 EAS exome AF: 0.0000335

Gnomad4 SAS exome AF: 0.00258

Gnomad4 FIN exome AF: 0.00462

Gnomad4 NFE exome AF: 0.0198

Gnomad4 OTH exome AF: 0.0162

GnomAD4 genome AF: 0.0135 AC: 1516 AN: 112035 Hom.: 32 Cov.: 23 AF XY: 0.0120 AC XY: 411 AN XY: 34215

Gnomad4 AFR AF: 0.00220

Gnomad4 AMR AF: 0.0239

Gnomad4 ASJ AF: 0.00908

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00185

Gnomad4 FIN AF: 0.00347

Gnomad4 NFE AF: 0.0184

Gnomad4 OTH AF: 0.0144

Alfa AF: 0.0139 Hom.: 105

Bravo AF: 0.0147

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 18, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 23, 2017	- -

Developmental and epileptic encephalopathy, 36 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2016

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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.5
DANN	Benign	0.91
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: rs5985637; hg19: chrX-110963338; COSMIC: COSV52639057;