rs2270969

chr3-183037179-A-G

Variant summary

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

The NM_020166.5(MCCC1):c.1594+39T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0411 in 1,601,662 control chromosomes in the GnomAD database, including 2,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (542 hom., cov: 31)
  • Exomes 𝑓: 0.038 (1874 hom.)
• Consequence: MCCC1 NM_020166.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.60

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=-0.81).
• BP6: Variant 3-183037179-A-G is Benign according to our data. Variant chr3-183037179-A-G is described in ClinVar as [Benign]. Clinvar id is 261206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCCC1	NM_020166.5	c.1594+39T>C		intron_variant		ENST00000265594.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCCC1	ENST00000265594.9	c.1594+39T>C		intron_variant		1	NM_020166.5	P1

Frequencies

GnomAD3 genomes AF: 0.0677 AC: 10289 AN: 151976 Hom.: 538 Cov.: 31

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0574

Gnomad FIN AF: 0.0527

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0274

Gnomad OTH AF: 0.0665

GnomAD3 exomes AF: 0.0622 AC: 15605 AN: 250792 Hom.: 815 AF XY: 0.0567 AC XY: 7689 AN XY: 135664

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.0421

Gnomad EAS exome AF: 0.0886

Gnomad SAS exome AF: 0.0589

Gnomad FIN exome AF: 0.0545

Gnomad NFE exome AF: 0.0277

Gnomad OTH exome AF: 0.0547

GnomAD4 exome AF: 0.0383 AC: 55563 AN: 1449568 Hom.: 1874 Cov.: 28 AF XY: 0.0380 AC XY: 27433 AN XY: 721776

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.0427

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.0540

Gnomad4 FIN exome AF: 0.0552

Gnomad4 NFE exome AF: 0.0259

Gnomad4 OTH exome AF: 0.0464

GnomAD4 genome AF: 0.0678 AC: 10305 AN: 152094 Hom.: 542 Cov.: 31 AF XY: 0.0694 AC XY: 5159 AN XY: 74348

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0568

Gnomad4 FIN AF: 0.0527

Gnomad4 NFE AF: 0.0273

Gnomad4 OTH AF: 0.0668

Alfa AF: 0.0366 Hom.: 311

Bravo AF: 0.0749

Asia WGS AF: 0.0990 AC: 345 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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3-methylcrotonyl-CoA carboxylase 1 deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.8
Dann	Benign	0.65

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: rs2270969; hg19: chr3-182754967;