Variant chr12-109554327-C-G 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.*2701G>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 0.281 in 453,820 control chromosomes in the GnomAD database, including 19,874 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 9024 hom., cov: 32)

Exomes 𝑓: 0.26 ( 10850 hom. )

Consequence

MMAB
NM_052845.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.413

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 12-109554327-C-G is Benign according to our data. Variant chr12-109554327-C-G is described in ClinVar as [Benign]. Clinvar id is 307009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 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.*2701G>C		3_prime_UTR_variant	9/9	ENST00000545712.7	NP_443077.1	Q96EY8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMAB	ENST00000545712 linkuse as main transcript	c.*2701G>C		3_prime_UTR_variant	9/9	1	NM_052845.4	ENSP00000445920.1		Q96EY8

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49326

AN:

151910

Hom.:

8996

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.257

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.317

GnomAD3 exomes

AF:

0.265

AC:

34608

AN:

130478

Hom.:

4952

AF XY:

0.259

AC XY:

18411

AN XY:

71222

show subpopulations

Gnomad AFR exome

AF:

0.508

Gnomad AMR exome

AF:

0.289

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.210

Gnomad SAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.181

Gnomad NFE exome

AF:

0.276

Gnomad OTH exome

AF:

0.268

GnomAD4 exome

AF:

0.259

AC:

78154

AN:

301792

Hom.:

10850

Cov.:

AF XY:

0.251

AC XY:

43126

AN XY:

171992

show subpopulations

Gnomad4 AFR exome

AF:

0.502

Gnomad4 AMR exome

AF:

0.290

Gnomad4 ASJ exome

AF:

0.263

Gnomad4 EAS exome

AF:

0.214

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.186

Gnomad4 NFE exome

AF:

0.271

Gnomad4 OTH exome

AF:

0.269

GnomAD4 genome

AF:

0.325

AC:

49406

AN:

152028

Hom.:

9024

Cov.:

AF XY:

0.316

AC XY:

23514

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.502

Gnomad4 AMR

AF:

0.298

Gnomad4 ASJ

AF:

0.257

Gnomad4 EAS

AF:

0.206

Gnomad4 SAS

AF:

0.177

Gnomad4 FIN

AF:

0.178

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.319

Alfa

AF:

0.292

Hom.:

1302

Bravo

AF:

0.346

Asia WGS

AF:

0.217

AC:

756

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.5

DANN

Benign

0.33

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