rs9381786

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000255.4(MMUT):c.1676+77A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,178,926 control chromosomes in the GnomAD database, including 35,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3841 hom., cov: 32)

Exomes 𝑓: 0.24 ( 31588 hom. )

Consequence

MMUT
NM_000255.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.539

Publications

9 publications found

Variant links:

Genes affected

MMUT (HGNC:7526): (methylmalonyl-CoA mutase) This gene encodes the mitochondrial enzyme methylmalonyl Coenzyme A mutase. In humans, the product of this gene is a vitamin B12-dependent enzyme which catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA, while in other species this enzyme may have different functions. Mutations in this gene may lead to various types of methylmalonic aciduria. [provided by RefSeq, Jul 2008]

MMUT Gene-Disease associations (from GenCC):

methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
vitamin B12-unresponsive methylmalonic acidemia type mut-
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
vitamin B12-unresponsive methylmalonic acidemia type mut0
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MMUT 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=-0.75).

BP6

Variant 6-49444562-T-G is Benign according to our data. Variant chr6-49444562-T-G is described in ClinVar as Benign. ClinVar VariationId is 498783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMUT	NM_000255.4 link	c.1676+77A>C		intron_variant	Intron 9 of 12	ENST00000274813.4	NP_000246.2	P22033A0A024RD82B2R6K1
MMUT	XM_005249143.4 link	c.1676+77A>C		intron_variant	Intron 9 of 12		XP_005249200.1	P22033A0A024RD82

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMUT	ENST00000274813.4 link	c.1676+77A>C		intron_variant	Intron 9 of 12	1	NM_000255.4	ENSP00000274813.3		P22033

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33392

AN:

151956

Hom.:

3838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.317

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.241

Gnomad SAS

AF:

0.279

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.220

GnomAD4 exome

AF:

0.244

AC:

250114

AN:

1026852

Hom.:

31588

AF XY:

0.247

AC XY:

131215

AN XY:

530514

show subpopulations

African (AFR)

AF:

0.165

AC:

4147

AN:

25128

American (AMR)

AF:

0.126

AC:

5539

AN:

43936

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

4412

AN:

23334

East Asian (EAS)

AF:

0.207

AC:

7801

AN:

37646

South Asian (SAS)

AF:

0.284

AC:

21970

AN:

77406

European-Finnish (FIN)

AF:

0.229

AC:

11315

AN:

49328

Middle Eastern (MID)

AF:

0.291

AC:

1429

AN:

4918

European-Non Finnish (NFE)

AF:

0.254

AC:

182401

AN:

719120

Other (OTH)

AF:

0.241

AC:

11100

AN:

46036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

9592

19184

28777

38369

47961

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4788

9576

14364

19152

23940

<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:

0.220

AC:

33408

AN:

152074

Hom.:

3841

Cov.:

AF XY:

0.219

AC XY:

16242

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.166

AC:

6890

AN:

41470

American (AMR)

AF:

0.174

AC:

2652

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

650

AN:

3472

East Asian (EAS)

AF:

0.241

AC:

1243

AN:

5166

South Asian (SAS)

AF:

0.277

AC:

1337

AN:

4824

European-Finnish (FIN)

AF:

0.230

AC:

2430

AN:

10580

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17383

AN:

67982

Other (OTH)

AF:

0.218

AC:

459

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1320

2640

3959

5279

6599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<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:

0.244

Hom.:

2489

Bravo

AF:

0.211

Asia WGS

AF:

0.204

AC:

708

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27884173, 21671183) -

Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency

Benign:2

Jan 06, 2022

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 19, 2021

Pars Genome Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jan 06, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency

Benign:1

Aug 28, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.7

(source)

DANN

Benign

0.80

PhyloP100

0.54

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over