MCCC1 p.Ile678Ile

Variant names:

• chr3-183017280-C-C
• NM_020166.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr3-183017281--
• chr3-183017281-G-A
• chr3-183017281-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020166.5(MCCC1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MCCC1 NM_020166.5 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990
• Publications: 0 publications found

Genes affected

MCCC1 (HGNC:6936): (methylcrotonyl-CoA carboxylase subunit 1) This gene encodes the large 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. [provided by RefSeq, Jul 2008]

MCCC1-AS1 (HGNC:40366): (MCCC1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020166.5. 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
	MCCC1	NM_020166.5	MANE Select	c.		exon_region	Exon 18 of 19	NP_064551.3
	MCCC1	NM_001363880.1		c.		exon_region	Exon 17 of 18	NP_001350809.1	E9PHF7
	MCCC1	NM_001293273.2		c.		exon_region	Exon 16 of 17	NP_001280202.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCCC1	ENST00000265594.9	TSL:1 MANE Select	c.		exon_region	Exon 18 of 19	ENSP00000265594.4	Q96RQ3
	MCCC1	ENST00000492597.5	TSL:1	c.		exon_region	Exon 17 of 18	ENSP00000419898.1	E9PHF7
	MCCC1	ENST00000497830.5	TSL:1	n.		exon_region	Exon 16 of 17	ENSP00000420088.1	F2Z3E2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.099

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-182735068;