chr2-71124445-G-C

Position:

• chr2-71124445-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032601.4(MCEE):​c.139C>G​(p.Arg47Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000752 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: MCEE NM_032601.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.53

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCEE	NM_032601.4	c.139C>G	p.Arg47Gly	missense_variant	2/3	ENST00000244217.6	NP_115990.3
MCEE	XM_047446039.1	c.139C>G	p.Arg47Gly	missense_variant	2/3		XP_047301995.1
MCEE	XM_005264613.3	c.139C>G	p.Arg47Gly	missense_variant	2/3		XP_005264670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCEE	ENST00000244217.6	c.139C>G	p.Arg47Gly	missense_variant	2/3	1	NM_032601.4	ENSP00000244217.5
MCEE	ENST00000413592.5	c.7C>G	p.Arg3Gly	missense_variant	1/2	2		ENSP00000391140.1
MCEE	ENST00000486135.1	c.-147C>G		5_prime_UTR_variant	3/3	3		ENSP00000441569.1
MCEE	ENST00000494660.6	c.-147C>G		5_prime_UTR_variant	2/2	2		ENSP00000437361.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251162 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135822

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461834 Hom.: 0 Cov.: 34 AF XY: 0.00000825 AC XY: 6 AN XY: 727212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.38	T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.6	.;M
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Uncertain	0.47
Sift	Benign	0.050	D;D
Sift4G	Uncertain	0.057	T;D
Polyphen		0.99	.;D
Vest4		0.68
MutPred		0.73		.;Loss of solvent accessibility (P = 0.0769);
MVP		0.81
MPC		0.50
ClinPred		0.98	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.78
gMVP		0.78

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: rs111033538; hg19: chr2-71351575;