dbSNP rs886061556: MMUT:c.*200A>T (chr6-49431528-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000255.4(MMUT):c.*200A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

MMUT
NM_000255.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.714

Publications

0 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, G2P, Labcorp Genetics (formerly Invitae)
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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000255.4. 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
	MMUT	NM_000255.4	MANE Select	c.*200A>T		3_prime_UTR	Exon 13 of 13	NP_000246.2	P22033

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MMUT	ENST00000274813.4	TSL:1 MANE Select	c.*200A>T	3_prime_UTR	Exon 13 of 13	ENSP00000274813.3	P22033
MMUT	ENST00000878067.1		c.*200A>T	splice_region	Exon 13 of 13	ENSP00000548126.1
MMUT	ENST00000878066.1		c.*200A>T	splice_region	Exon 12 of 12	ENSP00000548125.1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

62596

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000662

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000240

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000439

AC:

AN:

318978

Hom.:

Cov.:

AF XY:

0.0000589

AC XY:

AN XY:

169638

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

9112

American (AMR)

AF:

0.000157

AC:

AN:

12762

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9130

East Asian (EAS)

AF:

0.00

AC:

AN:

19988

South Asian (SAS)

AF:

0.0000287

AC:

AN:

34848

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23954

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1320

European-Non Finnish (NFE)

AF:

0.0000472

AC:

AN:

190526

Other (OTH)

AF:

0.000115

AC:

AN:

17338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000112

AC:

AN:

62642

Hom.:

Cov.:

AF XY:

0.000194

AC XY:

AN XY:

30960

show subpopulations

African (AFR)

AF:

0.0000660

AC:

AN:

15152

American (AMR)

AF:

0.000239

AC:

AN:

8372

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1358

East Asian (EAS)

AF:

0.00

AC:

AN:

3140

South Asian (SAS)

AF:

0.00

AC:

AN:

1868

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4090

Middle Eastern (MID)

AF:

0.00

AC:

AN:

176

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

27136

Other (OTH)

AF:

0.00

AC:

AN:

942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000142

Hom.:

Bravo

AF:

0.0000491

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.0

(source)

DANN

Benign

0.75

PhyloP100

0.71

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