2-71109848-TCA-T

Variant names:

• chr2-71109848-TCA-T
• rs146624706
• NM_032601.4:c.*120_*121delTG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_032601.4(MCEE):​c.*120_*121delTG 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
• Publications: 1 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: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

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.*120_*121delTG		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.*120_*121delTG		3_prime_UTR	Exon 3 of 3	ENSP00000244217.5	Q96PE7
	MCEE	ENST00000413592.5	TSL:2	c.*120_*121delTG		3_prime_UTR	Exon 2 of 2	ENSP00000391140.1	H7BZS7
	MCEE	ENST00000916433.1		c.*120_*121delTG		3_prime_UTR	Exon 2 of 2	ENSP00000586492.1

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

African (AFR) AF: 0.134 AC: 2182 AN: 16242

American (AMR) AF: 0.00918 AC: 259 AN: 28222

Ashkenazi Jewish (ASJ) AF: 0.00120 AC: 23 AN: 19092

East Asian (EAS) AF: 0.00567 AC: 183 AN: 32298

South Asian (SAS) AF: 0.0122 AC: 687 AN: 56212

European-Finnish (FIN) AF: 0.0000858 AC: 3 AN: 34954

Middle Eastern (MID) AF: 0.0147 AC: 46 AN: 3120

European-Non Finnish (NFE) AF: 0.00244 AC: 992 AN: 406538

Other (OTH) AF: 0.0160 AC: 515 AN: 32152

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

African (AFR) AF: 0.134 AC: 5567 AN: 41530

American (AMR) AF: 0.0169 AC: 258 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00982 AC: 51 AN: 5192

South Asian (SAS) AF: 0.0122 AC: 59 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00275 AC: 187 AN: 68006

Other (OTH) AF: 0.0279 AC: 59 AN: 2114

Alfa AF: 0.0328 Hom.: 34

Bravo AF: 0.0468

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Methylmalonic acidemia (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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: rs146624706; hg19: chr2-71336978;