Variant 13-52012447-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001004127.3(ALG11):c.29T>G(p.Leu10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,760 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ALG11
NM_001004127.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.96

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG11	NM_001004127.3 link	c.29T>G	p.Leu10Arg	missense_variant	Exon 1 of 4	ENST00000521508.2	NP_001004127.2	Q2TAA5
ALG11	NR_036571.3 link	n.50T>G		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG11	ENST00000521508.2 link	c.29T>G	p.Leu10Arg	missense_variant	Exon 1 of 4	1	NM_001004127.3	ENSP00000430236.1		Q2TAA5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251030

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00000205

AC:

AN:

1461760

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

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

Cov.:

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.12

.;.;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.36

T;T;T

M_CAP

Benign

0.083

MetaRNN

Uncertain

0.64

D;D;D

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.3

.;.;M

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-6.0

D;.;N

REVEL

Benign

0.29

Sift

Uncertain

0.0040

.;.;D

Sift4G

Uncertain

0.0060

.;.;D

Polyphen

0.23

.;.;B

Vest4

0.81

MutPred

0.47

Gain of catalytic residue at K12 (P = 0.0028);Gain of catalytic residue at K12 (P = 0.0028);Gain of catalytic residue at K12 (P = 0.0028);

MVP

0.80

MPC

0.19

ClinPred

0.97

GERP RS

3.9

Varity_R

0.41

gMVP

0.87

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over