chr12-109561047-C-A
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_052845.4(MMAB):c.577G>T(p.Glu193*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. E193E) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MMAB
NM_052845.4 stop_gained
NM_052845.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 5.67
Publications
13 publications found
Genes affected
MMAB (HGNC:19331): (metabolism of cobalamin associated B) This gene encodes a protein that catalyzes the final step in the conversion of vitamin B(12) into adenosylcobalamin (AdoCbl), a vitamin B12-containing coenzyme for methylmalonyl-CoA mutase. Mutations in the gene are the cause of vitamin B12-dependent methylmalonic aciduria linked to the cblB complementation group. Alternatively spliced transcript variants have been found. [provided by RefSeq, Apr 2011]
MMAB Gene-Disease associations (from GenCC):
- methylmalonic aciduria, cblB typeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 12-109561047-C-A is Pathogenic according to our data. Variant chr12-109561047-C-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3574199.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
30
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1448210Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 720600
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1448210
Hom.:
Cov.:
36
AF XY:
AC XY:
0
AN XY:
720600
African (AFR)
AF:
AC:
0
AN:
33212
American (AMR)
AF:
AC:
0
AN:
44412
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25788
East Asian (EAS)
AF:
AC:
0
AN:
39108
South Asian (SAS)
AF:
AC:
0
AN:
86160
European-Finnish (FIN)
AF:
AC:
0
AN:
48606
Middle Eastern (MID)
AF:
AC:
0
AN:
5714
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1105504
Other (OTH)
AF:
AC:
0
AN:
59706
GnomAD4 genome
GnomAD4 genome
Cov.:
30
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Methylmalonic aciduria, cblB type Pathogenic:1
Jan 03, 2024
Fulgent Genetics, Fulgent Genetics
Significance:Likely pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
PhyloP100
Vest4
GERP RS
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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