rs753556936

Positions:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP3BP6BS1BS2

The NM_001099922.3(ALG13):c.880C>G(p.Pro294Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000914 in 1,202,944 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P294S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000082 ( 0 hom. 6 hem. )

Consequence

ALG13
NM_001099922.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 6.07

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 -8 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.765

BP6

Variant X-111711720-C-G is Benign according to our data. Variant chrX-111711720-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 589561.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00000825 (9/1091078) while in subpopulation AMR AF= 0.000259 (9/34762). AF 95% confidence interval is 0.000134. There are 0 homozygotes in gnomad4_exome. There are 6 alleles in male gnomad4_exome subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Hemizygotes in GnomAdExome4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG13	NM_001099922.3 linkuse as main transcript	c.880C>G	p.Pro294Ala	missense_variant	6/27	ENST00000394780.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG13	ENST00000394780.8 linkuse as main transcript	c.880C>G	p.Pro294Ala	missense_variant	6/27	2	NM_001099922.3	A2	Q9NP73-1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111866

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34102

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000947

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000278

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000404

AC:

AN:

173246

Hom.:

AF XY:

0.0000488

AC XY:

AN XY:

61488

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000270

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000825

AC:

AN:

1091078

Hom.:

Cov.:

AF XY:

0.0000168

AC XY:

AN XY:

357022

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000259

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111866

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34102

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000947

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000278

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.0000333

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2017

The p.P294A variant (also known as c.880C>G), located in coding exon 6 of the ALG13 gene, results from a C to G substitution at nucleotide position 880. The proline at codon 294 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Developmental and epileptic encephalopathy, 36

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

D;.;.;.;.

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

D;D;.;D;.

M_CAP

Pathogenic

0.59

MetaRNN

Pathogenic

0.76

D;D;D;D;D

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.4

M;.;.;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-6.3

D;.;D;.;.

REVEL

Benign

0.22

Sift

Uncertain

0.010

D;.;D;.;.

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

D;D;D;D;D

Vest4

0.76

MutPred

0.23

Loss of glycosylation at P294 (P = 0.0692);.;.;.;.;

MVP

0.50

MPC

0.70

ClinPred

0.59

GERP RS

5.7

Varity_R

0.50

gMVP

0.39

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