5-71626789-G-C

Variant names:

• chr5-71626789-G-C
• rs12516456
• NM_022132.5:c.738+36G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022132.5(MCCC2):​c.738+36G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MCCC2 NM_022132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729
• Publications: 11 publications found

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]

MCCC2 Gene-Disease associations (from GenCC):

• 3-methylcrotonyl-CoA carboxylase 2 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 3-methylcrotonyl-CoA carboxylase deficiency

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022132.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCCC2	NM_022132.5	MANE Select	c.738+36G>C		intron	N/A	NP_071415.1
	MCCC2	NM_001363147.1		c.625-5332G>C		intron	N/A	NP_001350076.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCCC2	ENST00000340941.11	TSL:1 MANE Select	c.738+36G>C		intron	N/A	ENSP00000343657.6
	MCCC2	ENST00000509358.7	TSL:1	c.738+36G>C		intron	N/A	ENSP00000420994.3
	MCCC2	ENST00000629193.3	TSL:1	c.625-5332G>C		intron	N/A	ENSP00000486535.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 87483

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.45
PhyloP100		-0.73

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: rs12516456; hg19: chr5-70922616;