Variant 13-52012419-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_001004127.3(ALG11):c.1A>G(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.000000684 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ALG11
NM_001004127.3 start_lost

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.90

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 Pathogenic. Variant got 12 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 13-52012419-A-G is Pathogenic according to our data. Variant chr13-52012419-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1028907.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG11	NM_001004127.3 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	1/4	ENST00000521508.2	NP_001004127.2
ALG11	NR_036571.3 linkuse as main transcript	n.22A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG11	ENST00000521508.2 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	1/4	1	NM_001004127.3	ENSP00000430236	P4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ALG11-congenital disorder of glycosylation

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Baylor Genetics

Aug 27, 2019

This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.47

BayesDel_noAF

Pathogenic

0.44

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.064

.;.;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Pathogenic

0.92

MetaRNN

Pathogenic

0.99

D;D;D

MetaSVM

Benign

-0.46

MutationTaster

Benign

1.0

D;D

PROVEAN

Uncertain

-4.0

D;.;N

REVEL

Uncertain

0.50

Sift

Pathogenic

0.0

.;.;D

Sift4G

Pathogenic

0.0

.;.;D

Polyphen

0.71

.;.;P

Vest4

0.83

MutPred

0.99

Gain of catalytic residue at A3 (P = 2e-04);Gain of catalytic residue at A3 (P = 2e-04);Gain of catalytic residue at A3 (P = 2e-04);

MVP

0.80

ClinPred

0.99

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.93

gMVP

0.68

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