5-71635139-A-G

Position:

chr5-71635139-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022132.5(MCCC2):c.904-12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,613,564 control chromosomes in the GnomAD database, including 107,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8664 hom., cov: 32)

Exomes 𝑓: 0.36 ( 98805 hom. )

Consequence

MCCC2
NM_022132.5 intron

Scores

Splicing: ADA: 0.00006331

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.82

Variant links:

Genes affected

MCCC2 (HGNC:6937): (methylcrotonyl-CoA carboxylase subunit 2) This gene encodes the small 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. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2018]

MCCC2 links:

MCCC2 (HGNC:):

MCCC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 5-71635139-A-G is Benign according to our data. Variant chr5-71635139-A-G is described in ClinVar as [Benign]. Clinvar id is 96032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-71635139-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCCC2	NM_022132.5 linkuse as main transcript	c.904-12A>G		intron_variant		ENST00000340941.11	NP_071415.1	Q9HCC0-1A0A140VK29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCCC2	ENST00000340941.11 linkuse as main transcript	c.904-12A>G		intron_variant		1	NM_022132.5	ENSP00000343657.6		Q9HCC0-1

Frequencies

GnomAD3 genomes

AF:

0.313

AC:

47594

AN:

152014

Hom.:

8660

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.178

Gnomad AMR

AF:

0.506

Gnomad ASJ

AF:

0.459

Gnomad EAS

AF:

0.524

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.348

GnomAD3 exomes

AF:

0.383

AC:

96393

AN:

251374

Hom.:

20774

AF XY:

0.375

AC XY:

50901

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.127

Gnomad AMR exome

AF:

0.631

Gnomad ASJ exome

AF:

0.450

Gnomad EAS exome

AF:

0.526

Gnomad SAS exome

AF:

0.285

Gnomad FIN exome

AF:

0.291

Gnomad NFE exome

AF:

0.360

Gnomad OTH exome

AF:

0.391

GnomAD4 exome

AF:

0.360

AC:

526268

AN:

1461432

Hom.:

98805

Cov.:

AF XY:

0.358

AC XY:

260286

AN XY:

727044

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.617

Gnomad4 ASJ exome

AF:

0.458

Gnomad4 EAS exome

AF:

0.529

Gnomad4 SAS exome

AF:

0.288

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.357

Gnomad4 OTH exome

AF:

0.360

GnomAD4 genome

AF:

0.313

AC:

47603

AN:

152132

Hom.:

8664

Cov.:

AF XY:

0.314

AC XY:

23374

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.506

Gnomad4 ASJ

AF:

0.459

Gnomad4 EAS

AF:

0.525

Gnomad4 SAS

AF:

0.301

Gnomad4 FIN

AF:

0.281

Gnomad4 NFE

AF:

0.359

Gnomad4 OTH

AF:

0.346

Alfa

AF:

0.345

Hom.:

2151

Bravo

AF:

0.328

Asia WGS

AF:

0.386

AC:

1340

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 10, 2014	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

3-methylcrotonyl-CoA carboxylase 2 deficiency

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 19, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0010

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000063

dbscSNV1_RF

Benign

0.052

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over