13-52012444-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_StrongBS1

The NM_001004127.3(ALG11):​c.26G>T​(p.Cys9Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C9S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

ALG11
NM_001004127.3 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.223
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 Likely_benign. Variant got -6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06171295).
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00013 (190/1461752) while in subpopulation SAS AF= 0.00022 (19/86204). AF 95% confidence interval is 0.000144. There are 0 homozygotes in gnomad4_exome. There are 86 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALG11NM_001004127.3 linkc.26G>T p.Cys9Phe missense_variant Exon 1 of 4 ENST00000521508.2 NP_001004127.2 Q2TAA5
ALG11NR_036571.3 linkn.47G>T 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.26G>T p.Cys9Phe missense_variant Exon 1 of 4 1 NM_001004127.3 ENSP00000430236.1 Q2TAA5

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152230
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000996
AC:
25
AN:
251050
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135824
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000199
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000882
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000130
AC:
190
AN:
1461752
Hom.:
0
Cov.:
30
AF XY:
0.000118
AC XY:
86
AN XY:
727148
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000230
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000220
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000138
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152348
Hom.:
0
Cov.:
33
AF XY:
0.0000805
AC XY:
6
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.0000721
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000727
Hom.:
0
Bravo
AF:
0.000132
ExAC
AF:
0.0000906
AC:
11
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.057
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
12
DANN
Benign
0.75
DEOGEN2
Benign
0.087
.;.;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.31
T;T;T
M_CAP
Benign
0.052
D
MetaRNN
Benign
0.062
T;T;T
MetaSVM
Benign
-0.67
T
MutationAssessor
Uncertain
2.6
.;.;M
PrimateAI
Benign
0.27
T
PROVEAN
Pathogenic
-11
D;.;N
REVEL
Benign
0.19
Sift
Benign
0.095
.;.;T
Sift4G
Uncertain
0.020
.;.;D
Polyphen
0.063
.;.;B
Vest4
0.57
MutPred
0.52
Gain of catalytic residue at E5 (P = 0.0067);Gain of catalytic residue at E5 (P = 0.0067);Gain of catalytic residue at E5 (P = 0.0067);
MVP
0.40
MPC
0.078
ClinPred
0.16
T
GERP RS
0.14
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.056
gMVP
0.54

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.

Other links and lift over

dbSNP: rs200041400; hg19: chr13-52586580; API