chr13-52024053-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 16/21 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

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

ALG11-congenital disorder of glycosylation
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, ClinGen, Ambry Genetics, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ALG11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004127.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG11	NM_001004127.3	MANE Select	c.323A>G	p.Asn108Ser	missense	Exon 3 of 4	NP_001004127.2
	ALG11	NR_036571.3		n.66-4266A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ALG11	ENST00000521508.2	TSL:1 MANE Select	c.323A>G	p.Asn108Ser	missense	Exon 3 of 4	ENSP00000430236.1
ALG11	ENST00000649340.2		c.323A>G	p.Asn108Ser	missense	Exon 3 of 4	ENSP00000497184.2
ALG11	ENST00000681053.1		c.92A>G	p.Asn31Ser	missense	Exon 2 of 3	ENSP00000505307.1

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

GnomAD2 exomes

AF:

0.0266

AC:

6700

AN:

251414

AF XY:

0.0224

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 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

African (AFR)

AF:

0.00487

AC:

163

AN:

33480

American (AMR)

AF:

0.132

AC:

5909

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00608

AC:

159

AN:

26134

East Asian (EAS)

AF:

0.000453

AC:

AN:

39696

South Asian (SAS)

AF:

0.0125

AC:

1077

AN:

86256

European-Finnish (FIN)

AF:

0.00307

AC:

164

AN:

53420

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0114

AC:

12649

AN:

1111988

Other (OTH)

AF:

0.0120

AC:

723

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

1066

2132

3198

4264

5330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

554

1108

1662

2216

2770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0156

AC:

2374

AN:

152236

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

1225

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.00636

AC:

264

AN:

41542

American (AMR)

AF:

0.0804

AC:

1229

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3472

East Asian (EAS)

AF:

0.000965

AC:

AN:

5184

South Asian (SAS)

AF:

0.0112

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0107

AC:

731

AN:

68010

Other (OTH)

AF:

0.0123

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

112

224

336

448

560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0141

Hom.:

151

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

ALG11-congenital disorder of glycosylation (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.63

CADD

Benign

3.8

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.055

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

PhyloP100

1.5

PrimateAI

Benign

0.38

PROVEAN

Benign

1.0

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

0.94

Polyphen

0.0

Vest4

0.0020

MPC

0.039

ClinPred

0.0034

GERP RS

-1.8

Varity_R

0.016

gMVP

0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over