2-71109708-C-T

Variant names:

• chr2-71109708-C-T
• rs72903553
• NM_032601.4:c.*262G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032601.4(MCEE):​c.*262G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0276 in 244,234 control chromosomes in the GnomAD database, including 399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (382 hom., cov: 31)
  • Exomes 𝑓: 0.0060 (17 hom.)
• Consequence: MCEE NM_032601.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.791

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 2-71109708-C-T is Benign according to our data. Variant chr2-71109708-C-T is described in ClinVar as [Benign]. Clinvar id is 336933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCEE	NM_032601.4	c.*262G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000244217.6	NP_115990.3
MCEE	XM_005264613.3	c.*262G>A		3_prime_UTR_variant	Exon 3 of 3		XP_005264670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCEE	ENST00000244217	c.*262G>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_032601.4	ENSP00000244217.5
MCEE	ENST00000413592	c.*262G>A		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000391140.1

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6187 AN: 151942 Hom.: 380 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00982

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.00275

Gnomad OTH AF: 0.0283

GnomAD4 exome AF: 0.00598 AC: 551 AN: 92174 Hom.: 17 Cov.: 0 AF XY: 0.00583 AC XY: 308 AN XY: 52786

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.00962

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00603

Gnomad4 SAS exome AF: 0.0101

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00222

Gnomad4 OTH exome AF: 0.0124

GnomAD4 genome AF: 0.0407 AC: 6190 AN: 152060 Hom.: 382 Cov.: 31 AF XY: 0.0389 AC XY: 2889 AN XY: 74328

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0168

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00984

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00275

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.0205 Hom.: 37

Bravo AF: 0.0468

Asia WGS AF: 0.0150 AC: 52 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.8
DANN	Benign	0.59

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: rs72903553; hg19: chr2-71336838;