2-71109848-TCA-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_032601.4(MCEE):c.*120_*121del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 781,070 control chromosomes in the GnomAD database, including 571 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (378 hom., cov: 30)
  • Exomes 𝑓: 0.0078 (193 hom.)
• Consequence: MCEE NM_032601.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.119

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 -16 ACMG points.

• BP6: Variant 2-71109848-TCA-T is Benign according to our data. Variant chr2-71109848-TCA-T is described in ClinVar as [Likely_benign]. Clinvar id is 336934.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/exons	MANE	UniProt
MCEE	NM_032601.4	c.*120_*121del		3_prime_UTR_variant	3/3	ENST00000244217.6
MCEE	XM_005264613.3	c.*120_*121del		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCEE	ENST00000244217.6	c.*120_*121del		3_prime_UTR_variant	3/3	1	NM_032601.4	P1
MCEE	ENST00000413592.5	c.*120_*121del		3_prime_UTR_variant	2/2	2
MCEE	ENST00000462609.2	n.597_598del		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6185 AN: 152122 Hom.: 376 Cov.: 30

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00980

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00275

Gnomad OTH AF: 0.0282

GnomAD4 exome AF: 0.00778 AC: 4890 AN: 628830 Hom.: 193 AF XY: 0.00725 AC XY: 2417 AN XY: 333338

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.00918

Gnomad4 ASJ exome AF: 0.00120

Gnomad4 EAS exome AF: 0.00567

Gnomad4 SAS exome AF: 0.0122

Gnomad4 FIN exome AF: 0.0000858

Gnomad4 NFE exome AF: 0.00244

Gnomad4 OTH exome AF: 0.0160

GnomAD4 genome AF: 0.0406 AC: 6188 AN: 152240 Hom.: 378 Cov.: 30 AF XY: 0.0388 AC XY: 2890 AN XY: 74456

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00982

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00275

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0328 Hom.: 34

Bravo AF: 0.0468

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 16, 2018

- -

Methylmalonic acidemia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs146624706; hg19: chr2-71336978;