2-71109906-T-G

Variant names:

• chr2-71109906-T-G
• rs1672850658
• NM_032601.4:c.*64A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032601.4(MCEE):​c.*64A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,375,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: MCEE NM_032601.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09
• Publications: 0 publications found

Genes affected

MCEE (HGNC:16732): (methylmalonyl-CoA epimerase) The product of this gene catalyzes the interconversion of D- and L-methylmalonyl-CoA during the degradation of branched chain amino acids. odd chain-length fatty acids, and other metabolites. Mutations in this gene result in methylmalonyl-CoA epimerase deficiency, which is presented as mild to moderate methylmalonic aciduria. [provided by RefSeq, Jul 2008]

MCEE Gene-Disease associations (from GenCC):

• methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032601.4. 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
	MCEE	NM_032601.4	MANE Select	c.*64A>C		3_prime_UTR	Exon 3 of 3	NP_115990.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCEE	ENST00000244217.6	TSL:1 MANE Select	c.*64A>C		3_prime_UTR	Exon 3 of 3	ENSP00000244217.5	Q96PE7
	MCEE	ENST00000413592.5	TSL:2	c.*64A>C		3_prime_UTR	Exon 2 of 2	ENSP00000391140.1	H7BZS7
	MCEE	ENST00000916433.1		c.*64A>C		3_prime_UTR	Exon 2 of 2	ENSP00000586492.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1375504 Hom.: 0 Cov.: 20 AF XY: 0.00000145 AC XY: 1 AN XY: 689036

African (AFR) AF: 0.00 AC: 0 AN: 31814

American (AMR) AF: 0.00 AC: 0 AN: 44184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25566

East Asian (EAS) AF: 0.00 AC: 0 AN: 39236

South Asian (SAS) AF: 0.00 AC: 0 AN: 84264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5594

European-Non Finnish (NFE) AF: 9.61e-7 AC: 1 AN: 1040520

Other (OTH) AF: 0.00 AC: 0 AN: 57604

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.8
DANN	Benign	0.84
PhyloP100		1.1

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: rs1672850658; hg19: chr2-71337036;