3-183017331-C-T

Variant names:

• chr3-183017331-C-T
• rs1043492520
• NM_020166.5:c.1984G>A

Variant summary

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

The NM_020166.5(MCCC1):​c.1984G>A​(p.Val662Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V662F) 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: 6.31
• 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.1984G>A	p.Val662Ile	missense	Exon 18 of 19	NP_064551.3
	MCCC1	NM_001363880.1		c.1657G>A	p.Val553Ile	missense	Exon 17 of 18	NP_001350809.1	E9PHF7
	MCCC1	NM_001293273.2		c.1633G>A	p.Val545Ile	missense	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.1984G>A	p.Val662Ile	missense	Exon 18 of 19	ENSP00000265594.4	Q96RQ3
	MCCC1	ENST00000492597.5	TSL:1	c.1657G>A	p.Val553Ile	missense	Exon 17 of 18	ENSP00000419898.1	E9PHF7
	MCCC1	ENST00000497830.5	TSL:1	n.*1581G>A		non_coding_transcript_exon	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
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	0.0088	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.3
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.89	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.027	D
Polyphen		0.99	D
Vest4		0.46
MutPred		0.73		Gain of sheet (P = 0.0149)
MVP		0.64
MPC		0.55
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.20
gMVP		0.62
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1043492520; hg19: chr3-182735119;