Variant rs72650187 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_052845.4(MMAB):c.349-17T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00808 in 1,593,234 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 66 hom. )

Consequence

MMAB
NM_052845.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.557

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 12-109561869-A-G is Benign according to our data. Variant chr12-109561869-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 445771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-109561869-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00561 (855/152298) while in subpopulation NFE AF= 0.00972 (661/68018). AF 95% confidence interval is 0.0091. There are 2 homozygotes in gnomad4. There are 381 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMAB	NM_052845.4 linkuse as main transcript	c.349-17T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000545712.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMAB	ENST00000545712.7 linkuse as main transcript	c.349-17T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_052845.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00562

AC:

856

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00649

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00972

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00579

AC:

1240

AN:

214260

Hom.:

AF XY:

0.00599

AC XY:

693

AN XY:

115714

show subpopulations

Gnomad AFR exome

AF:

0.00140

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.000746

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00390

Gnomad FIN exome

AF:

0.00845

Gnomad NFE exome

AF:

0.00959

Gnomad OTH exome

AF:

0.00547

GnomAD4 exome

AF:

0.00834

AC:

12017

AN:

1440936

Hom.:

Cov.:

AF XY:

0.00819

AC XY:

5854

AN XY:

715020

show subpopulations

Gnomad4 AFR exome

AF:

0.00130

Gnomad4 AMR exome

AF:

0.00131

Gnomad4 ASJ exome

AF:

0.000777

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00385

Gnomad4 FIN exome

AF:

0.00965

Gnomad4 NFE exome

AF:

0.00971

Gnomad4 OTH exome

AF:

0.00648

GnomAD4 genome

AF:

0.00561

AC:

855

AN:

152298

Hom.:

Cov.:

AF XY:

0.00512

AC XY:

381

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00649

Gnomad4 NFE

AF:

0.00972

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00731

Hom.:

Bravo

AF:

0.00496

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Methylmalonic aciduria, cblB type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 29, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Aug 03, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over