13-52012420-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_SupportingPM2PP5

The NM_001004127.3(ALG11):ā€‹c.2T>Cā€‹(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,814 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 (no stars).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000062 ( 0 hom. )

Consequence

ALG11
NM_001004127.3 start_lost

Scores

7
5
4

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.34
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1
Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 186 CDS bases. Genomic position: 52019054. Lost 0.126 part of the original CDS.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 13-52012420-T-C is Pathogenic according to our data. Variant chr13-52012420-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1184605.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALG11NM_001004127.3 linkc.2T>C p.Met1? start_lost Exon 1 of 4 ENST00000521508.2 NP_001004127.2 Q2TAA5
ALG11NR_036571.3 linkn.23T>C non_coding_transcript_exon_variant Exon 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ALG11ENST00000521508.2 linkc.2T>C p.Met1? start_lost Exon 1 of 4 1 NM_001004127.3 ENSP00000430236.1 Q2TAA5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461814
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727192
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:
0.00000809
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

ALG11-congenital disorder of glycosylation Pathogenic:1
-
Genomics England Pilot Project, Genomics England
Significance: Likely pathogenic
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.44
CADD
Benign
22
DANN
Benign
0.92
DEOGEN2
Benign
0.064
.;.;T
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Pathogenic
0.91
D
MetaRNN
Pathogenic
0.99
D;D;D
MetaSVM
Benign
-0.34
T
PROVEAN
Pathogenic
-6.0
D;.;N
REVEL
Uncertain
0.54
Sift
Pathogenic
0.0
.;.;D
Sift4G
Pathogenic
0.0
.;.;D
Polyphen
0.93
.;.;P
Vest4
0.86
MutPred
0.98
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
0.88
ClinPred
1.0
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.92
gMVP
0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-52586556; API