X-111681210-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001099922.3(ALG13):c.-9A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000537 in 1,207,791 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 202 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 0.00023 ( 0 hom., 10 hem., cov: 24)

Exomes 𝑓: 0.00057 ( 0 hom. 192 hem. )

Consequence

ALG13
NM_001099922.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.08

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant X-111681210-A-G is Benign according to our data. Variant chrX-111681210-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 387664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000234 (26/111293) while in subpopulation SAS AF= 0.000759 (2/2634). AF 95% confidence interval is 0.000266. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG13	NM_001099922.3 linkuse as main transcript	c.-9A>G		5_prime_UTR_variant	1/27	ENST00000394780.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG13	ENST00000394780.8 linkuse as main transcript	c.-9A>G		5_prime_UTR_variant	1/27	2	NM_001099922.3	A2	Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.000234

AC:

AN:

111293

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

33693

show subpopulations

Gnomad AFR

AF:

0.0000980

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000759

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000398

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000285

AC:

AN:

182745

Hom.:

AF XY:

0.000238

AC XY:

AN XY:

67229

show subpopulations

Gnomad AFR exome

AF:

0.000305

Gnomad AMR exome

AF:

0.000184

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000264

Gnomad FIN exome

AF:

0.0000626

Gnomad NFE exome

AF:

0.000453

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000567

AC:

622

AN:

1096498

Hom.:

Cov.:

AF XY:

0.000531

AC XY:

192

AN XY:

361918

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000444

Gnomad4 FIN exome

AF:

0.0000494

Gnomad4 NFE exome

AF:

0.000663

Gnomad4 OTH exome

AF:

0.000717

GnomAD4 genome

AF:

0.000234

AC:

AN:

111293

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

33693

show subpopulations

Gnomad4 AFR

AF:

0.0000980

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000759

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000398

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000391

Hom.:

Bravo

AF:

0.000264

EpiCase

AF:

0.000655

EpiControl

AF:

0.000416

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 01, 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. -

ALG13-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 30, 2019

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

Cadd

Benign

Dann

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

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

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