2-71110073-C-T

Position:

chr2-71110073-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032601.4(MCEE):c.428G>A(p.Arg143His) variant causes a missense change. The variant allele was found at a frequency of 0.00845 in 1,613,128 control chromosomes in the GnomAD database, including 395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R143C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.024 ( 112 hom., cov: 31)

Exomes 𝑓: 0.0069 ( 283 hom. )

Consequence

MCEE
NM_032601.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.14

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035372078).

BP6

Variant 2-71110073-C-T is Benign according to our data. Variant chr2-71110073-C-T is described in ClinVar as [Benign]. Clinvar id is 336936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-71110073-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCEE	NM_032601.4 linkuse as main transcript	c.428G>A	p.Arg143His	missense_variant	3/3	ENST00000244217.6	NP_115990.3
MCEE	XM_005264613.3 linkuse as main transcript	c.266G>A	p.Arg89His	missense_variant	3/3		XP_005264670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MCEE	ENST00000244217.6 linkuse as main transcript	c.428G>A	p.Arg143His	missense_variant	3/3	1	NM_032601.4	ENSP00000244217	P1
MCEE	ENST00000413592.5 linkuse as main transcript	c.134G>A	p.Arg45His	missense_variant	2/2	2		ENSP00000391140
MCEE	ENST00000462609.2 linkuse as main transcript	n.374G>A		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes

AF:

0.0235

AC:

3578

AN:

152064

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0643

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0374

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00980

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00265

Gnomad OTH

AF:

0.0226

GnomAD3 exomes

AF:

0.0189

AC:

4749

AN:

251110

Hom.:

183

AF XY:

0.0155

AC XY:

2107

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.0662

Gnomad AMR exome

AF:

0.0813

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.00799

Gnomad SAS exome

AF:

0.0119

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00227

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.00688

AC:

10050

AN:

1460946

Hom.:

283

Cov.:

AF XY:

0.00654

AC XY:

4750

AN XY:

726816

show subpopulations

Gnomad4 AFR exome

AF:

0.0661

Gnomad4 AMR exome

AF:

0.0734

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.00580

Gnomad4 SAS exome

AF:

0.0125

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00222

Gnomad4 OTH exome

AF:

0.0110

GnomAD4 genome

AF:

0.0235

AC:

3583

AN:

152182

Hom.:

112

Cov.:

AF XY:

0.0219

AC XY:

1627

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0642

Gnomad4 AMR

AF:

0.0375

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00983

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00265

Gnomad4 OTH

AF:

0.0223

Alfa

AF:

0.00489

Hom.:

Bravo

AF:

0.0307

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.0583

AC:

257

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.0178

AC:

2157

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.00393

EpiControl

AF:

0.00290

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2015

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

D;D

MetaRNN

Benign

0.0035

T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Pathogenic

3.3

.;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-4.6

D;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

.;D

Vest4

0.18

MPC

0.58

ClinPred

0.067

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.45

gMVP

0.85

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over