rs78599682

chr12-109561016-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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]

ACMG classification

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: 10028 AN: 127884 Hom.: 361 Cov.: 26

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.0511

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.0673

Gnomad EAS AF: 0.0363

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0927

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0745

Gnomad OTH AF: 0.0912

GnomAD3 exomes AF: 0.0693 AC: 16796 AN: 242440 Hom.: 637 AF XY: 0.0730 AC XY: 9649 AN XY: 132224

Gnomad AFR exome AF: 0.0678

Gnomad AMR exome AF: 0.0475

Gnomad ASJ exome AF: 0.0848

Gnomad EAS exome AF: 0.0323

Gnomad SAS exome AF: 0.112

Gnomad FIN exome AF: 0.0612

Gnomad NFE exome AF: 0.0702

Gnomad OTH exome AF: 0.0727

GnomAD4 exome AF: 0.101 AC: 99574 AN: 990240 Hom.: 3808 Cov.: 30 AF XY: 0.102 AC XY: 51225 AN XY: 503040

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.0570

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.0413

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.0848

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.0784 AC: 10033 AN: 127964 Hom.: 361 Cov.: 26 AF XY: 0.0810 AC XY: 4939 AN XY: 60962

Gnomad4 AFR AF: 0.0816

Gnomad4 AMR AF: 0.0804

Gnomad4 ASJ AF: 0.0673

Gnomad4 EAS AF: 0.0362

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0927

Gnomad4 NFE AF: 0.0745

Gnomad4 OTH AF: 0.0902

Alfa AF: 0.0697 Hom.: 74

Bravo AF: 0.0689

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Methylmalonic aciduria, cblB type Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jul 01, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	7.0
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs78599682; hg19: chr12-109998821;