rs5985637

Positions:

chrX-111720110-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001099922.3(ALG13):c.1266T>C(p.Gly422Gly) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.78

Variant links:

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 links:

ALG13 (HGNC:):

ALG13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.1266T>C	p.Gly422Gly	synonymous_variant	11/27	ENST00000394780.8	NP_001093392.1	Q9NP73-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG13	ENST00000394780.8 linkuse as main transcript	c.1266T>C	p.Gly422Gly	synonymous_variant	11/27	2	NM_001099922.3	ENSP00000378260.3		Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

1515

AN:

111980

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

410

AN XY:

34150

show subpopulations

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.:

AF XY:

0.00957

AC XY:

431

AN XY:

45028

show subpopulations

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.:

AF XY:

0.0158

AC XY:

5476

AN XY:

346094

show subpopulations

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.:

Cov.:

AF XY:

0.0120

AC XY:

411

AN XY:

34215

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 23, 2017	- -
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. -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over