dbSNP rs140592995: MMAA:c.-66+36G>C (chr4-145619443-G-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_172250.3(MMAA):c.-66+36G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00732 in 152,336 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0073 ( 12 hom., cov: 32)

Exomes 𝑓: 0.027 ( 0 hom. )

Consequence

MMAA
NM_172250.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.60

Publications

0 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: Myriad Women’s Health, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P

MMAA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

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

BP6

Variant 4-145619443-G-C is Benign according to our data. Variant chr4-145619443-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1326747.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency = 0.0714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMAA	NM_172250.3 link	c.-66+36G>C		intron_variant	Intron 1 of 6	ENST00000649156.2	NP_758454.1	Q8IVH4
MMAA	NM_001375644.1 link	c.-272G>C		5_prime_UTR_variant	Exon 1 of 7		NP_001362573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMAA	ENST00000649156.2 link	c.-66+36G>C		intron_variant	Intron 1 of 6		NM_172250.3	ENSP00000497008.1		Q8IVH4

Frequencies

GnomAD3 genomes

AF:

0.00732

AC:

1113

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00952

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00786

Gnomad FIN

AF:

0.0146

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00716

GnomAD4 exome

AF:

0.0270

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0200

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.0714

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0185

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00731

AC:

1113

AN:

152262

Hom.:

Cov.:

AF XY:

0.00721

AC XY:

537

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

41550

American (AMR)

AF:

0.00588

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00952

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00787

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0146

AC:

155

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0103

AC:

698

AN:

68006

Other (OTH)

AF:

0.00709

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

107

161

214

268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00725

Hom.:

Bravo

AF:

0.00671

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 24, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.024

(source)

DANN

Benign

0.44

PhyloP100

-3.6

PromoterAI

-0.11

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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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rs140592995

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over