rs11067231

Variant names:

• chr12-109555798-C-A
• rs11067231
• NM_052845.4:c.*1230G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-109555798-C-A
• chr12-109555798-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_052845.4(MMAB):​c.*1230G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 453,606 control chromosomes in the GnomAD database, including 65,034 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25399 hom., cov: 30)
  • Exomes 𝑓: 0.50 (39635 hom.)
• Consequence: MMAB NM_052845.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.10
• Publications: 26 publications found

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 Gene-Disease associations (from GenCC):

• methylmalonic acidemia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• methylmalonic aciduria, cblB type

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-109555798-C-A is Benign according to our data. Variant chr12-109555798-C-A is described in ClinVar as Benign. ClinVar VariationId is 307039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052845.4. 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
	MMAB	NM_052845.4	MANE Select	c.*1230G>T		3_prime_UTR	Exon 9 of 9	NP_443077.1	Q96EY8
	MMAB	NR_038118.2		n.2094G>T		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMAB	ENST00000545712.7	TSL:1 MANE Select	c.*1230G>T		3_prime_UTR	Exon 9 of 9	ENSP00000445920.1	Q96EY8

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85968 AN: 151704 Hom.: 25355 Cov.: 30

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.580

GnomAD2 exomes AF: 0.491 AC: 64022 AN: 130508 AF XY: 0.487

Gnomad AFR exome AF: 0.737

Gnomad AMR exome AF: 0.462

Gnomad ASJ exome AF: 0.551

Gnomad EAS exome AF: 0.298

Gnomad FIN exome AF: 0.465

Gnomad NFE exome AF: 0.538

Gnomad OTH exome AF: 0.505

GnomAD4 exome AF: 0.505 AC: 152368 AN: 301784 Hom.: 39635 Cov.: 0 AF XY: 0.498 AC XY: 85657 AN XY: 171986

African (AFR) AF: 0.729 AC: 6237 AN: 8554

American (AMR) AF: 0.465 AC: 12687 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 5970 AN: 10786

East Asian (EAS) AF: 0.301 AC: 2776 AN: 9210

South Asian (SAS) AF: 0.423 AC: 25232 AN: 59648

European-Finnish (FIN) AF: 0.470 AC: 5810 AN: 12368

Middle Eastern (MID) AF: 0.601 AC: 691 AN: 1150

European-Non Finnish (NFE) AF: 0.540 AC: 85716 AN: 158754

Other (OTH) AF: 0.516 AC: 7249 AN: 14040

GnomAD4 genome AF: 0.567 AC: 86074 AN: 151822 Hom.: 25399 Cov.: 30 AF XY: 0.557 AC XY: 41328 AN XY: 74222

African (AFR) AF: 0.724 AC: 29976 AN: 41420

American (AMR) AF: 0.503 AC: 7666 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1846 AN: 3464

East Asian (EAS) AF: 0.297 AC: 1528 AN: 5140

South Asian (SAS) AF: 0.389 AC: 1869 AN: 4808

European-Finnish (FIN) AF: 0.463 AC: 4872 AN: 10522

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.536 AC: 36396 AN: 67906

Other (OTH) AF: 0.581 AC: 1223 AN: 2106

Alfa AF: 0.554 Hom.: 66934

Bravo AF: 0.580

Asia WGS AF: 0.385 AC: 1337 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Methylmalonic aciduria, cblB type (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.086
DANN	Benign	0.48
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11067231; hg19: chr12-109993603; COSMIC: COSV108027807; COSMIC: COSV108027807;