Variant 12-109554193-A-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.*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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.523

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:

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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 12-109554193-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_multiple_submitters_no_conflicts, 2 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 linkuse as main transcript	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 linkuse as main transcript	c.*2835T>C		3_prime_UTR_variant	9/9	1	NM_052845.4	P1

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25771

AN:

152010

Hom.:

2263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0989

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.172

GnomAD3 exomes

AF:

0.162

AC:

21111

AN:

130236

Hom.:

1767

AF XY:

0.162

AC XY:

11539

AN XY:

71122

show subpopulations

Gnomad AFR exome

AF:

0.185

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.186

Gnomad EAS exome

AF:

0.147

Gnomad SAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.109

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.163

AC:

49028

AN:

300996

Hom.:

4199

Cov.:

AF XY:

0.160

AC XY:

27454

AN XY:

171388

show subpopulations

Gnomad4 AFR exome

AF:

0.184

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.188

Gnomad4 EAS exome

AF:

0.147

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.112

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.168

GnomAD4 genome

AF:

0.169

AC:

25781

AN:

152128

Hom.:

2260

Cov.:

AF XY:

0.164

AC XY:

12203

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.189

Gnomad4 AMR

AF:

0.156

Gnomad4 ASJ

AF:

0.191

Gnomad4 EAS

AF:

0.140

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.0989

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.175

Alfa

AF:

0.177

Hom.:

736

Bravo

AF:

0.176

Asia WGS

AF:

0.153

AC:

531

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 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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.7

DANN

Benign

0.62

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