Genetic Variant MMAB:c.*2701G>C (chr12-109554327-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

methylmalonic acidemia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
methylmalonic aciduria, cblB type
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Myriad Women’s Health, G2P

MMAB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052845.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMAB	NM_052845.4	MANE Select	c.*2701G>C		3_prime_UTR	Exon 9 of 9	NP_443077.1	Q96EY8
	MMAB	NR_038118.2		n.3565G>C		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMAB	ENST00000545712.7	TSL:1 MANE Select	c.*2701G>C		3_prime_UTR	Exon 9 of 9	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

GnomAD2 exomes

AF:

0.265

AC:

34608

AN:

130478

AF XY:

0.259

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 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

African (AFR)

AF:

0.502

AC:

4293

AN:

8554

American (AMR)

AF:

0.290

AC:

7915

AN:

27274

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

2833

AN:

10786

East Asian (EAS)

AF:

0.214

AC:

1973

AN:

9210

South Asian (SAS)

AF:

0.196

AC:

11677

AN:

59650

European-Finnish (FIN)

AF:

0.186

AC:

2302

AN:

12364

Middle Eastern (MID)

AF:

0.314

AC:

361

AN:

1150

European-Non Finnish (NFE)

AF:

0.271

AC:

43028

AN:

158760

Other (OTH)

AF:

0.269

AC:

3772

AN:

14044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

5139

10278

15416

20555

25694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

294

588

882

1176

1470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.325

AC:

49406

AN:

152028

Hom.:

9024

Cov.:

AF XY:

0.316

AC XY:

23514

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.502

AC:

20777

AN:

41428

American (AMR)

AF:

0.298

AC:

4552

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

891

AN:

3472

East Asian (EAS)

AF:

0.206

AC:

1066

AN:

5164

South Asian (SAS)

AF:

0.177

AC:

854

AN:

4824

European-Finnish (FIN)

AF:

0.178

AC:

1882

AN:

10592

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.270

AC:

18328

AN:

67960

Other (OTH)

AF:

0.319

AC:

673

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1621

3241

4862

6482

8103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.292

Hom.:

1302

Bravo

AF:

0.346

Asia WGS

AF:

0.217

AC:

756

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Methylmalonic aciduria, cblB type (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.5

(source)

DANN

Benign

0.33

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over