chr4-102657873-A-G
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_005908.4(MANBA):c.1513T>C(p.Ser505Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,946 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
MANBA
NM_005908.4 missense
NM_005908.4 missense
Scores
14
4
1
Clinical Significance
Conservation
PhyloP100: 8.77
Publications
7 publications found
Genes affected
MANBA (HGNC:6831): (mannosidase beta) This gene encodes a member of the glycosyl hydrolase 2 family. The encoded protein localizes to the lysosome where it is the final exoglycosidase in the pathway for N-linked glycoprotein oligosaccharide catabolism. Mutations in this gene are associated with beta-mannosidosis, a lysosomal storage disease that has a wide spectrum of neurological involvement. [provided by RefSeq, Jul 2008]
MANBA Gene-Disease associations (from GenCC):
- beta-mannosidosisInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp, Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.974
PP5
Variant 4-102657873-A-G is Pathogenic according to our data. Variant chr4-102657873-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 1679.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MANBA | NM_005908.4 | c.1513T>C | p.Ser505Pro | missense_variant | Exon 12 of 17 | ENST00000647097.2 | NP_005899.3 | |
MANBA | XM_047415692.1 | c.1438T>C | p.Ser480Pro | missense_variant | Exon 13 of 18 | XP_047271648.1 | ||
MANBA | XM_047415693.1 | c.1438T>C | p.Ser480Pro | missense_variant | Exon 13 of 18 | XP_047271649.1 | ||
MANBA | XM_047415694.1 | c.865T>C | p.Ser289Pro | missense_variant | Exon 8 of 13 | XP_047271650.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1460946Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726866 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1460946
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
726866
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33450
American (AMR)
AF:
AC:
0
AN:
44712
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26124
East Asian (EAS)
AF:
AC:
0
AN:
39688
South Asian (SAS)
AF:
AC:
0
AN:
86230
European-Finnish (FIN)
AF:
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111202
Other (OTH)
AF:
AC:
0
AN:
60366
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<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 Cov.: 32
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Beta-D-mannosidosis Pathogenic:1
Aug 01, 2008
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
.;D;D;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
.;H;H;.;.
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;D;.;.;D
REVEL
Pathogenic
Sift
Pathogenic
.;D;.;.;D
Sift4G
Pathogenic
.;D;.;.;D
Polyphen
1.0
.;D;D;.;D
Vest4
0.97, 0.98
MutPred
Loss of glycosylation at T508 (P = 0.0221);Loss of glycosylation at T508 (P = 0.0221);Loss of glycosylation at T508 (P = 0.0221);.;.;
MVP
0.98
MPC
0.48
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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