rs78599682
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_052845.4(MMAB):c.584+24A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 1,118,204 control chromosomes in the GnomAD database, including 4,169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.078 ( 361 hom., cov: 26)
Exomes 𝑓: 0.10 ( 3808 hom. )
Consequence
MMAB
NM_052845.4 intron
NM_052845.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.300
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 12-109561016-T-C is Benign according to our data. Variant chr12-109561016-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 262248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MMAB | NM_052845.4 | c.584+24A>G | intron_variant | ENST00000545712.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MMAB | ENST00000545712.7 | c.584+24A>G | intron_variant | 1 | NM_052845.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0784 AC: 10028AN: 127884Hom.: 361 Cov.: 26
GnomAD3 genomes
?
AF:
AC:
10028
AN:
127884
Hom.:
Cov.:
26
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0693 AC: 16796AN: 242440Hom.: 637 AF XY: 0.0730 AC XY: 9649AN XY: 132224
GnomAD3 exomes
AF:
AC:
16796
AN:
242440
Hom.:
AF XY:
AC XY:
9649
AN XY:
132224
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.101 AC: 99574AN: 990240Hom.: 3808 Cov.: 30 AF XY: 0.102 AC XY: 51225AN XY: 503040
GnomAD4 exome
AF:
AC:
99574
AN:
990240
Hom.:
Cov.:
30
AF XY:
AC XY:
51225
AN XY:
503040
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0784 AC: 10033AN: 127964Hom.: 361 Cov.: 26 AF XY: 0.0810 AC XY: 4939AN XY: 60962
GnomAD4 genome
?
AF:
AC:
10033
AN:
127964
Hom.:
Cov.:
26
AF XY:
AC XY:
4939
AN XY:
60962
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
180
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Methylmalonic aciduria, cblB type Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | Jul 01, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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