Variant rs78599682 details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.300

Variant links:

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 links:

MMAB (HGNC:):

MMAB links:

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	Protein	UniProt
MMAB	NM_052845.4 linkuse as main transcript	c.584+24A>G		intron_variant		ENST00000545712.7	NP_443077.1	Q96EY8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMAB	ENST00000545712.7 linkuse as main transcript	c.584+24A>G		intron_variant		1	NM_052845.4	ENSP00000445920.1		Q96EY8

Frequencies

GnomAD3 genomes

AF:

0.0784

AC:

10028

AN:

127884

Hom.:

361

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.102

AC XY:

51225

AN XY:

503040

show subpopulations

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.:

AF XY:

0.0810

AC XY:

4939

AN XY:

60962

show subpopulations

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.:

Bravo

AF:

0.0689

Asia WGS

AF:

0.0520

AC:

180

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over