3-183042285-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020166.5(MCCC1):c.1084-535A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,204 control chromosomes in the GnomAD database, including 4,476 homozygotes. 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: 𝑓 0.23 (4476 hom., cov: 33)
• Consequence: MCCC1 NM_020166.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCCC1	NM_020166.5	c.1084-535A>C		intron_variant		ENST00000265594.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCCC1	ENST00000265594.9	c.1084-535A>C		intron_variant		1	NM_020166.5	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34250 AN: 152086 Hom.: 4461 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.225 AC: 34288 AN: 152204 Hom.: 4476 Cov.: 33 AF XY: 0.231 AC XY: 17211 AN XY: 74410

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.217

Alfa AF: 0.209 Hom.: 5312

Bravo AF: 0.234

Asia WGS AF: 0.412 AC: 1430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.69
Dann	Benign	0.48

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: rs10513789; hg19: chr3-182760073;