3-183017291-AT-CG

Variant names:

• chr3-183017291-AT-CG
• NM_020166.5:c.2023_2024delATinsCG
• MCCC1 p.Met675Arg

Variant summary

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

The NM_020166.5(MCCC1):​c.2023_2024delATinsCG​(p.Met675Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M675T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MCCC1 NM_020166.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.12
• 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 0 ACMG points.

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.2023_2024delATinsCG	p.Met675Arg	missense	N/A	NP_064551.3
	MCCC1	NM_001363880.1		c.1696_1697delATinsCG	p.Met566Arg	missense	N/A	NP_001350809.1	E9PHF7
	MCCC1	NM_001293273.2		c.1672_1673delATinsCG	p.Met558Arg	missense	N/A	NP_001280202.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCCC1	ENST00000265594.9	TSL:1 MANE Select	c.2023_2024delATinsCG	p.Met675Arg	missense	N/A	ENSP00000265594.4	Q96RQ3
	MCCC1	ENST00000492597.5	TSL:1	c.1696_1697delATinsCG	p.Met566Arg	missense	N/A	ENSP00000419898.1	E9PHF7
	MCCC1	ENST00000497830.5	TSL:1	n.*1620_*1621delATinsCG		non_coding_transcript_exon	Exon 16 of 17	ENSP00000420088.1	F2Z3E2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.1

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: chr3-182735079;