chr5-71587309-A-G

Position:

• chr5-71587309-A-G

Variant summary

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

The ENST00000682727.1(MCCC2):​c.-117A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 1,445,368 control chromosomes in the GnomAD database, including 493,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (47353 hom., cov: 33)
  • Exomes 𝑓: 0.83 (445733 hom.)
• Consequence: MCCC2 ENST00000682727.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0310

Genes affected

MCCC2 (HGNC:6937): (methylcrotonyl-CoA carboxylase subunit 2) This gene encodes the small subunit of 3-methylcrotonyl-CoA carboxylase. This enzyme functions as a heterodimer and catalyzes the carboxylation of 3-methylcrotonyl-CoA to form 3-methylglutaconyl-CoA. Mutations in this gene are associated with 3-Methylcrotonylglycinuria, an autosomal recessive disorder of leucine catabolism. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2018]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-71587309-A-G is Benign according to our data. Variant chr5-71587309-A-G is described in ClinVar as [Benign]. Clinvar id is 1175310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCCC2	NM_022132.5			upstream_gene_variant		ENST00000340941.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCCC2	ENST00000340941.11			upstream_gene_variant		1	NM_022132.5	P1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119131 AN: 152068 Hom.: 47331 Cov.: 33

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.814

GnomAD4 exome AF: 0.829 AC: 1072514 AN: 1293182 Hom.: 445733 Cov.: 23 AF XY: 0.830 AC XY: 522975 AN XY: 630114

Gnomad4 AFR exome AF: 0.629

Gnomad4 AMR exome AF: 0.887

Gnomad4 ASJ exome AF: 0.900

Gnomad4 EAS exome AF: 0.878

Gnomad4 SAS exome AF: 0.826

Gnomad4 FIN exome AF: 0.820

Gnomad4 NFE exome AF: 0.831

Gnomad4 OTH exome AF: 0.828

GnomAD4 genome AF: 0.783 AC: 119211 AN: 152186 Hom.: 47353 Cov.: 33 AF XY: 0.786 AC XY: 58479 AN XY: 74404

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.811

Alfa AF: 0.813 Hom.: 9787

Bravo AF: 0.782

Asia WGS AF: 0.826 AC: 2873 AN: 3478

ClinVar

Significance: 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

Mar 03, 2015

- -

3-methylcrotonyl-CoA carboxylase 2 deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.4
DANN	Benign	0.63

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: rs11746722; hg19: chr5-70883136;