rs139631003

Positions:

• chrX-111686132-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001099922.3(ALG13):​c.383+1029A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,116,505 control chromosomes in the GnomAD database, including 5 homozygotes. There are 331 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (4 hom., 174 hem., cov: 23)
  • Exomes 𝑓: 0.00061 (1 hom. 157 hem.)
• Consequence: ALG13 NM_001099922.3 intron
• Scores: Splicing: ADA: 0.00001616
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.51

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant X-111686132-A-G is Benign according to our data. Variant chrX-111686132-A-G is described in ClinVar as [Benign]. Clinvar id is 382136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00581 (653/112378) while in subpopulation AFR AF= 0.0198 (614/30960). AF 95% confidence interval is 0.0185. There are 4 homozygotes in gnomad4. There are 174 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG13	NM_001099922.3	c.383+1029A>G		intron_variant		ENST00000394780.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG13	ENST00000394780.8	c.383+1029A>G		intron_variant		2	NM_001099922.3	A2

Frequencies

GnomAD3 genomes AF: 0.00575 AC: 646 AN: 112336 Hom.: 4 Cov.: 23 AF XY: 0.00493 AC XY: 170 AN XY: 34500

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00273

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000150

Gnomad OTH AF: 0.00132

GnomAD3 exomes AF: 0.00134 AC: 102 AN: 75955 Hom.: 0 AF XY: 0.000543 AC XY: 10 AN XY: 18431

Gnomad AFR exome AF: 0.0167

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000185

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000280

Gnomad NFE exome AF: 0.0000922

Gnomad OTH exome AF: 0.000886

GnomAD4 exome AF: 0.000606 AC: 609 AN: 1004127 Hom.: 1 Cov.: 21 AF XY: 0.000500 AC XY: 157 AN XY: 313987

Gnomad4 AFR exome AF: 0.0187

Gnomad4 AMR exome AF: 0.00153

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000108

Gnomad4 OTH exome AF: 0.00103

GnomAD4 genome AF: 0.00581 AC: 653 AN: 112378 Hom.: 4 Cov.: 23 AF XY: 0.00504 AC XY: 174 AN XY: 34552

Gnomad4 AFR AF: 0.0198

Gnomad4 AMR AF: 0.00272

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000150

Gnomad4 OTH AF: 0.00130

Alfa AF: 0.00326 Hom.: 14

Bravo AF: 0.00638

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 06, 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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Dec 11, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.033
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs139631003; hg19: chrX-110929360;