rs17480245

Positions:

chr13-52024053-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001004127.3(ALG11):c.323A>G(p.Asn108Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,614,094 control chromosomes in the GnomAD database, including 673 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 71 hom., cov: 32)

Exomes 𝑓: 0.014 ( 602 hom. )

Consequence

ALG11
NM_001004127.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.54

Variant links:

Genes affected

ALG11 (HGNC:32456): (ALG11 alpha-1,2-mannosyltransferase) This gene encodes a GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase which is localized to the cytosolic side of the endoplasmic reticulum (ER) and catalyzes the transfer of the fourth and fifth mannose residue from GDP-mannose (GDP-Man) to Man3GlcNAc2-PP-dolichol and Man4GlcNAc2-PP-dolichol resulting in the production of Man5GlcNAc2-PP-dolichol. Mutations in this gene are associated with congenital disorder of glycosylation type Ip (CDGIP). This gene overlaps but is distinct from the UTP14, U3 small nucleolar ribonucleoprotein, homolog C (yeast) gene. A pseudogene of the GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase has been identified on chromosome 19. [provided by RefSeq, Aug 2010]

ALG11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014317036).

BP6

Variant 13-52024053-A-G is Benign according to our data. Variant chr13-52024053-A-G is described in ClinVar as [Benign]. Clinvar id is 196291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG11	NM_001004127.3 linkuse as main transcript	c.323A>G	p.Asn108Ser	missense_variant	3/4	ENST00000521508.2	NP_001004127.2
ALG11	NR_036571.3 linkuse as main transcript	n.66-4266A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG11	ENST00000521508.2 linkuse as main transcript	c.323A>G	p.Asn108Ser	missense_variant	3/4	1	NM_001004127.3	ENSP00000430236	P4

Frequencies

GnomAD3 genomes

AF:

0.0156

AC:

2370

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00630

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0807

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0266

AC:

6700

AN:

251414

Hom.:

426

AF XY:

0.0224

AC XY:

3045

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00554

Gnomad AMR exome

AF:

0.139

Gnomad ASJ exome

AF:

0.00605

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0118

Gnomad FIN exome

AF:

0.00254

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.0187

GnomAD4 exome

AF:

0.0143

AC:

20882

AN:

1461858

Hom.:

602

Cov.:

AF XY:

0.0137

AC XY:

9982

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00487

Gnomad4 AMR exome

AF:

0.132

Gnomad4 ASJ exome

AF:

0.00608

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.0125

Gnomad4 FIN exome

AF:

0.00307

Gnomad4 NFE exome

AF:

0.0114

Gnomad4 OTH exome

AF:

0.0120

GnomAD4 genome

AF:

0.0156

AC:

2374

AN:

152236

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

1225

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00636

Gnomad4 AMR

AF:

0.0804

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0112

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0134

Hom.:

Bravo

AF:

0.0211

TwinsUK

AF:

0.0121

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00499

AC:

ESP6500EA

AF:

0.0101

AC:

ExAC

AF:

0.0225

AC:

2727

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.00938

EpiControl

AF:

0.00931

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 08, 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	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Feb 13, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 07, 2015	- -

ALG11-congenital disorder of glycosylation

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

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

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.63

CADD

Benign

3.8

DANN

Benign

0.53

DEOGEN2

Benign

0.055

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.79

T;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

.;N

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.38

PROVEAN

Benign

1.0

.;N

REVEL

Benign

0.13

Sift

Benign

1.0

.;T

Sift4G

Benign

0.94

.;T

Polyphen

0.0

.;B

Vest4

0.0020

MPC

0.039

ClinPred

0.0034

GERP RS

-1.8

Varity_R

0.016

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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