rs937652

chr3-183099540-C-Gchr3-183099540-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000492597.5(MCCC1):c.-101-4935G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,429,106 control chromosomes in the GnomAD database, including 413,985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (32632 hom., cov: 34)
  • Exomes 𝑓: 0.77 (381353 hom.)
• Consequence: MCCC1 ENST00000492597.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.31

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 3-183099540-C-G is Benign according to our data. Variant chr3-183099540-C-G is described in ClinVar as [Benign]. Clinvar id is 344318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCCC1	NM_020166.5			upstream_gene_variant		ENST00000265594.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCCC1	ENST00000265594.9			upstream_gene_variant		1	NM_020166.5	P1

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92915 AN: 152114 Hom.: 32651 Cov.: 34

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.644

GnomAD4 exome AF: 0.766 AC: 978651 AN: 1276874 Hom.: 381353 Cov.: 19 AF XY: 0.769 AC XY: 486727 AN XY: 633204

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.508

Gnomad4 ASJ exome AF: 0.724

Gnomad4 EAS exome AF: 0.647

Gnomad4 SAS exome AF: 0.777

Gnomad4 FIN exome AF: 0.787

Gnomad4 NFE exome AF: 0.798

Gnomad4 OTH exome AF: 0.727

GnomAD4 genome AF: 0.610 AC: 92898 AN: 152232 Hom.: 32632 Cov.: 34 AF XY: 0.611 AC XY: 45449 AN XY: 74428

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.774

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.640

Alfa AF: 0.699 Hom.: 5040

Bravo AF: 0.575

Asia WGS AF: 0.642 AC: 2234 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Methylcrotonyl-CoA carboxylase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

3-methylcrotonyl-CoA carboxylase 1 deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	3.0
Dann	Benign	0.79

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: rs937652; hg19: chr3-182817328; COSMIC: COSV55606960; COSMIC: COSV55606960;