chr2-71109708-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 -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 VariationId 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.

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.*262G>A		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.*262G>A		3_prime_UTR	Exon 3 of 3	ENSP00000244217.5	Q96PE7
	MCEE	ENST00000413592.5	TSL:2	c.*262G>A		3_prime_UTR	Exon 2 of 2	ENSP00000391140.1	H7BZS7
	MCEE	ENST00000916433.1		c.*262G>A		3_prime_UTR	Exon 2 of 2	ENSP00000586492.1

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

African (AFR) AF: 0.121 AC: 190 AN: 1564

American (AMR) AF: 0.00962 AC: 43 AN: 4472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2142

East Asian (EAS) AF: 0.00603 AC: 31 AN: 5138

South Asian (SAS) AF: 0.0101 AC: 86 AN: 8502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3338

Middle Eastern (MID) AF: 0.00595 AC: 2 AN: 336

European-Non Finnish (NFE) AF: 0.00222 AC: 137 AN: 61690

Other (OTH) AF: 0.0124 AC: 62 AN: 4992

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

African (AFR) AF: 0.134 AC: 5572 AN: 41456

American (AMR) AF: 0.0168 AC: 256 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00984 AC: 51 AN: 5184

South Asian (SAS) AF: 0.0120 AC: 58 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.00275 AC: 187 AN: 68000

Other (OTH) AF: 0.0280 AC: 59 AN: 2106

Alfa AF: 0.0183 Hom.: 56

Bravo AF: 0.0468

Asia WGS AF: 0.0150 AC: 52 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.8
DANN	Benign	0.59
PhyloP100		0.79
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: rs72903553; hg19: chr2-71336838;