rs12817689
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_052845.4(MMAB):c.*2835T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 453,124 control chromosomes in the GnomAD database, including 6,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.17 ( 2260 hom., cov: 32)
Exomes 𝑓: 0.16 ( 4199 hom. )
Consequence
MMAB
NM_052845.4 3_prime_UTR
NM_052845.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.523
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 12-109554193-A-G is Benign according to our data. Variant chr12-109554193-A-G is described in ClinVar as [Benign]. Clinvar id is 307007.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MMAB | NM_052845.4 | c.*2835T>C | 3_prime_UTR_variant | 9/9 | ENST00000545712.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MMAB | ENST00000545712.7 | c.*2835T>C | 3_prime_UTR_variant | 9/9 | 1 | NM_052845.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.170 AC: 25771AN: 152010Hom.: 2263 Cov.: 32
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GnomAD3 exomes AF: 0.162 AC: 21111AN: 130236Hom.: 1767 AF XY: 0.162 AC XY: 11539AN XY: 71122
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GnomAD4 exome AF: 0.163 AC: 49028AN: 300996Hom.: 4199 Cov.: 0 AF XY: 0.160 AC XY: 27454AN XY: 171388
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GnomAD4 genome ? AF: 0.169 AC: 25781AN: 152128Hom.: 2260 Cov.: 32 AF XY: 0.164 AC XY: 12203AN XY: 74362
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Methylmalonic aciduria, cblB type Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at