dbSNP rs11067233: MMAB:c.*625G>C (chr12-109556403-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.*625G>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 0.245 in 453,852 control chromosomes in the GnomAD database, including 14,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4575 hom., cov: 31)

Exomes 𝑓: 0.25 ( 9667 hom. )

Consequence

MMAB
NM_052845.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.817

Publications

19 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=-0.8).

BP6

Variant 12-109556403-C-G is Benign according to our data. Variant chr12-109556403-C-G is described in ClinVar as Benign. ClinVar VariationId is 307053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 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.*625G>C		3_prime_UTR	Exon 9 of 9	NP_443077.1	Q96EY8
	MMAB	NR_038118.2		n.1489G>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.*625G>C		3_prime_UTR	Exon 9 of 9	ENSP00000445920.1	Q96EY8
	MMAB	ENST00000878519.1		c.*625G>C		downstream_gene	N/A	ENSP00000548578.1

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36684

AN:

151930

Hom.:

4570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.255

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.0911

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.277

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.262

GnomAD2 exomes

AF:

0.225

AC:

29420

AN:

130496

AF XY:

0.228

show subpopulations

Gnomad AFR exome

AF:

0.229

Gnomad AMR exome

AF:

0.173

Gnomad ASJ exome

AF:

0.291

Gnomad EAS exome

AF:

0.0885

Gnomad FIN exome

AF:

0.283

Gnomad NFE exome

AF:

0.263

Gnomad OTH exome

AF:

0.239

GnomAD4 exome

AF:

0.246

AC:

74258

AN:

301804

Hom.:

9667

Cov.:

AF XY:

0.247

AC XY:

42551

AN XY:

172002

show subpopulations

African (AFR)

AF:

0.227

AC:

1942

AN:

8552

American (AMR)

AF:

0.175

AC:

4769

AN:

27274

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

3140

AN:

10786

East Asian (EAS)

AF:

0.0872

AC:

803

AN:

9210

South Asian (SAS)

AF:

0.228

AC:

13572

AN:

59650

European-Finnish (FIN)

AF:

0.283

AC:

3506

AN:

12370

Middle Eastern (MID)

AF:

0.290

AC:

333

AN:

1150

European-Non Finnish (NFE)

AF:

0.269

AC:

42708

AN:

158766

Other (OTH)

AF:

0.248

AC:

3485

AN:

14046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

4697

9395

14092

18790

23487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

218

436

654

872

1090

<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:

0.241

AC:

36710

AN:

152048

Hom.:

4575

Cov.:

AF XY:

0.240

AC XY:

17848

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.221

AC:

9166

AN:

41448

American (AMR)

AF:

0.204

AC:

3123

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

957

AN:

3472

East Asian (EAS)

AF:

0.0913

AC:

473

AN:

5180

South Asian (SAS)

AF:

0.212

AC:

1020

AN:

4820

European-Finnish (FIN)

AF:

0.286

AC:

3021

AN:

10556

Middle Eastern (MID)

AF:

0.277

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.266

AC:

18087

AN:

67980

Other (OTH)

AF:

0.260

AC:

549

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1431

2861

4292

5722

7153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

380

760

1140

1520

1900

<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:

0.276

Hom.:

1166

Bravo

AF:

0.234

Asia WGS

AF:

0.165

AC:

575

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

-0.80

CADD

Benign

2.4

(source)

DANN

Benign

0.78

PhyloP100

-0.82

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

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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