rs12314392

Positions:

• chr12-109573061-A-G
• chr12-109573061-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000545712.7(MMAB):​c.134+286T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,080 control chromosomes in the GnomAD database, including 18,057 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.48 (18057 hom., cov: 32)
• Consequence: MMAB ENST00000545712.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.65

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-109573061-A-G is Benign according to our data. Variant chr12-109573061-A-G is described in ClinVar as [Benign]. Clinvar id is 680635.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMAB	NM_052845.4	c.134+286T>C		intron_variant		ENST00000545712.7	NP_443077.1
MMAB	NR_038118.2	n.158+286T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMAB	ENST00000545712.7	c.134+286T>C		intron_variant		1	NM_052845.4	ENSP00000445920	P1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72803 AN: 151962 Hom.: 18026 Cov.: 32

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.479 AC: 72896 AN: 152080 Hom.: 18057 Cov.: 32 AF XY: 0.472 AC XY: 35081 AN XY: 74330

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.491

Alfa AF: 0.464 Hom.: 11652

Bravo AF: 0.491

Asia WGS AF: 0.335 AC: 1165 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.48
DANN	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs12314392; hg19: chr12-110010866;