NM_000528.4:c.3009A>G
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000528.4(MAN2B1):c.3009A>G(p.Ser1003Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
MAN2B1
NM_000528.4 synonymous
NM_000528.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -6.88
Publications
0 publications found
Genes affected
MAN2B1 (HGNC:6826): (mannosidase alpha class 2B member 1) This gene encodes an enzyme that hydrolyzes terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides. Its activity is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover and it is member of family 38 of glycosyl hydrolases. The full length protein is processed in two steps. First, a 49 aa leader sequence is cleaved off and the remainder of the protein is processed into 3 peptides of 70 kDa, 42 kDa (D) and 13/15 kDa (E). Next, the 70 kDa peptide is further processed into three peptides (A, B and C). The A, B and C peptides are disulfide-linked. Defects in this gene have been associated with lysosomal alpha-mannosidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]
MAN2B1 Gene-Disease associations (from GenCC):
- alpha-mannosidosisInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Genomics England PanelApp, G2P, Laboratory for Molecular Medicine, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 19-12646647-T-C is Benign according to our data. Variant chr19-12646647-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2725705.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-6.89 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000528.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MAN2B1 | NM_000528.4 | MANE Select | c.3009A>G | p.Ser1003Ser | synonymous | Exon 24 of 24 | NP_000519.2 | O00754-1 | |
| MAN2B1 | NM_001440570.1 | c.3012A>G | p.Ser1004Ser | synonymous | Exon 24 of 24 | NP_001427499.1 | |||
| MAN2B1 | NM_001173498.2 | c.3006A>G | p.Ser1002Ser | synonymous | Exon 24 of 24 | NP_001166969.1 | O00754-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MAN2B1 | ENST00000456935.7 | TSL:1 MANE Select | c.3009A>G | p.Ser1003Ser | synonymous | Exon 24 of 24 | ENSP00000395473.2 | O00754-1 | |
| MAN2B1 | ENST00000221363.9 | TSL:1 | c.3006A>G | p.Ser1002Ser | synonymous | Exon 24 of 24 | ENSP00000221363.4 | O00754-2 | |
| ENSG00000269242 | ENST00000597692.1 | TSL:2 | n.567A>G | non_coding_transcript_exon | Exon 4 of 5 | ENSP00000470240.1 | M0QZ24 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461646Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727130 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461646
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727130
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33476
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111786
Other (OTH)
AF:
AC:
0
AN:
60384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
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2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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30-35
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
Deficiency of alpha-mannosidase (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
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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