dbSNP rs114699496: MMAA:c.-66+52C>T (chr4-145619459-C-T) – 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_001375644.1(MMAA):c.-256C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 152,320 control chromosomes in the GnomAD database, including 554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 553 hom., cov: 32)

Exomes 𝑓: 0.073 ( 1 hom. )

Consequence

MMAA
NM_001375644.1 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0120

Publications

2 publications found

Variant links:

Genes affected

MMAA (HGNC:18871): (metabolism of cobalamin associated A) The protein encoded by this gene is involved in the translocation of cobalamin into the mitochondrion, where it is used in the final steps of adenosylcobalamin synthesis. Adenosylcobalamin is a coenzyme required for the activity of methylmalonyl-CoA mutase. Defects in this gene are a cause of methylmalonic aciduria. [provided by RefSeq, Jul 2008]

MMAA Gene-Disease associations (from GenCC):

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

MMAA 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=-0.71).

BP6

Variant 4-145619459-C-T is Benign according to our data. Variant chr4-145619459-C-T is described in ClinVar as Benign. ClinVar VariationId is 1240548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375644.1. 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
	MMAA	NM_172250.3	MANE Select	c.-66+52C>T		intron	N/A	NP_758454.1	Q8IVH4
	MMAA	NM_001375644.1		c.-256C>T		5_prime_UTR	Exon 1 of 7	NP_001362573.1	Q8IVH4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MMAA	ENST00000649156.2	MANE Select	c.-66+52C>T	intron	N/A	ENSP00000497008.1	Q8IVH4
MMAA	ENST00000649704.1		c.-65-19616C>T	intron	N/A	ENSP00000497680.1	Q8IVH4
MMAA	ENST00000679563.1		c.-65-19616C>T	intron	N/A	ENSP00000506503.1	Q8IVH4

Frequencies

GnomAD3 genomes

AF:

0.0751

AC:

11429

AN:

152092

Hom.:

555

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0599

Gnomad ASJ

AF:

0.0403

Gnomad EAS

AF:

0.0885

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.0545

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0524

Gnomad OTH

AF:

0.0536

GnomAD4 exome

AF:

0.0727

AC:

AN:

110

Hom.:

AF XY:

0.0854

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.375

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0510

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0751

AC:

11436

AN:

152210

Hom.:

553

Cov.:

AF XY:

0.0758

AC XY:

5641

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.118

AC:

4887

AN:

41522

American (AMR)

AF:

0.0600

AC:

919

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0403

AC:

140

AN:

3470

East Asian (EAS)

AF:

0.0883

AC:

456

AN:

5166

South Asian (SAS)

AF:

0.148

AC:

713

AN:

4820

European-Finnish (FIN)

AF:

0.0545

AC:

579

AN:

10618

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0524

AC:

3561

AN:

67984

Other (OTH)

AF:

0.0530

AC:

112

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

541

1082

1623

2164

2705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0650

Hom.:

Bravo

AF:

0.0739

Asia WGS

AF:

0.110

AC:

383

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

3.7

(source)

DANN

Benign

0.96

PhyloP100

0.012

PromoterAI

0.12

Neutral

(source)

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over