Variant 12-109553880-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_052845.4(MMAB):c.*3148G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 453,906 control chromosomes in the GnomAD database, including 14,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.24 ( 4576 hom., cov: 33)

Exomes 𝑓: 0.25 ( 9671 hom. )

Consequence

MMAB
NM_052845.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.471

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 12-109553880-C-T is Benign according to our data. Variant chr12-109553880-C-T is described in ClinVar as [Benign]. Clinvar id is 307003.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMAB	NM_052845.4 linkuse as main transcript	c.*3148G>A		3_prime_UTR_variant	9/9	ENST00000545712.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMAB	ENST00000545712.7 linkuse as main transcript	c.*3148G>A		3_prime_UTR_variant	9/9	1	NM_052845.4	P1

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36722

AN:

151996

Hom.:

4571

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.0910

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.262

GnomAD3 exomes

AF:

0.226

AC:

29428

AN:

130484

Hom.:

3651

AF XY:

0.229

AC XY:

16278

AN XY:

71226

show subpopulations

Gnomad AFR exome

AF:

0.229

Gnomad AMR exome

AF:

0.173

Gnomad ASJ exome

AF:

0.291

Gnomad EAS exome

AF:

0.0882

Gnomad SAS exome

AF:

0.223

Gnomad FIN exome

AF:

0.284

Gnomad NFE exome

AF:

0.263

Gnomad OTH exome

AF:

0.239

GnomAD4 exome

AF:

0.246

AC:

74272

AN:

301792

Hom.:

9671

Cov.:

AF XY:

0.247

AC XY:

42559

AN XY:

171992

show subpopulations

Gnomad4 AFR exome

AF:

0.227

Gnomad4 AMR exome

AF:

0.175

Gnomad4 ASJ exome

AF:

0.291

Gnomad4 EAS exome

AF:

0.0869

Gnomad4 SAS exome

AF:

0.228

Gnomad4 FIN exome

AF:

0.283

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.248

GnomAD4 genome

AF:

0.242

AC:

36748

AN:

152114

Hom.:

4576

Cov.:

AF XY:

0.240

AC XY:

17867

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.221

Gnomad4 AMR

AF:

0.205

Gnomad4 ASJ

AF:

0.276

Gnomad4 EAS

AF:

0.0912

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.286

Gnomad4 NFE

AF:

0.266

Gnomad4 OTH

AF:

0.260

Alfa

AF:

0.258

Hom.:

2363

Bravo

AF:

0.234

Asia WGS

AF:

0.165

AC:

573

AN:

3478

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 13, 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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.57

DANN

Benign

0.84

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