chr12-109562388-C-T

Position:

• chr12-109562388-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052845.4(MMAB):​c.349-536G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,126 control chromosomes in the GnomAD database, including 25,478 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (25478 hom., cov: 33)
• Consequence: MMAB NM_052845.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMAB	NM_052845.4	c.349-536G>A		intron_variant		ENST00000545712.7	NP_443077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMAB	ENST00000545712.7	c.349-536G>A		intron_variant		1	NM_052845.4	ENSP00000445920.1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86140 AN: 152008 Hom.: 25434 Cov.: 33

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.581

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.567 AC: 86246 AN: 152126 Hom.: 25478 Cov.: 33 AF XY: 0.557 AC XY: 41419 AN XY: 74370

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.581

Alfa AF: 0.543 Hom.: 36195

Bravo AF: 0.581

Asia WGS AF: 0.383 AC: 1332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.15
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs7134594; hg19: chr12-110000193;