Variant chr5-71626789-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022132.5(MCCC2):c.738+36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 1,564,112 control chromosomes in the GnomAD database, including 544,577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 49906 hom., cov: 32)

Exomes 𝑓: 0.84 ( 494671 hom. )

Consequence

MCCC2
NM_022132.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.729

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 5-71626789-G-A is Benign according to our data. Variant chr5-71626789-G-A is described in ClinVar as [Benign]. Clinvar id is 261560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCCC2	NM_022132.5 linkuse as main transcript	c.738+36G>A		intron_variant		ENST00000340941.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCCC2	ENST00000340941.11 linkuse as main transcript	c.738+36G>A		intron_variant		1	NM_022132.5	P1	Q9HCC0-1

Frequencies

GnomAD3 genomes

AF:

0.807

AC:

122752

AN:

152100

Hom.:

49870

Cov.:

show subpopulations

Gnomad AFR

AF:

0.715

Gnomad AMI

AF:

0.789

Gnomad AMR

AF:

0.871

Gnomad ASJ

AF:

0.889

Gnomad EAS

AF:

0.872

Gnomad SAS

AF:

0.845

Gnomad FIN

AF:

0.818

Gnomad MID

AF:

0.864

Gnomad NFE

AF:

0.834

Gnomad OTH

AF:

0.833

GnomAD3 exomes

AF:

0.841

AC:

209654

AN:

249194

Hom.:

88400

AF XY:

0.841

AC XY:

113275

AN XY:

134746

show subpopulations

Gnomad AFR exome

AF:

0.710

Gnomad AMR exome

AF:

0.906

Gnomad ASJ exome

AF:

0.893

Gnomad EAS exome

AF:

0.877

Gnomad SAS exome

AF:

0.836

Gnomad FIN exome

AF:

0.826

Gnomad NFE exome

AF:

0.833

Gnomad OTH exome

AF:

0.853

GnomAD4 exome

AF:

0.837

AC:

1181085

AN:

1411894

Hom.:

494671

Cov.:

AF XY:

0.837

AC XY:

590273

AN XY:

705594

show subpopulations

Gnomad4 AFR exome

AF:

0.706

Gnomad4 AMR exome

AF:

0.903

Gnomad4 ASJ exome

AF:

0.897

Gnomad4 EAS exome

AF:

0.872

Gnomad4 SAS exome

AF:

0.834

Gnomad4 FIN exome

AF:

0.827

Gnomad4 NFE exome

AF:

0.835

Gnomad4 OTH exome

AF:

0.838

GnomAD4 genome

AF:

0.807

AC:

122847

AN:

152218

Hom.:

49906

Cov.:

AF XY:

0.810

AC XY:

60265

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.716

Gnomad4 AMR

AF:

0.871

Gnomad4 ASJ

AF:

0.889

Gnomad4 EAS

AF:

0.871

Gnomad4 SAS

AF:

0.846

Gnomad4 FIN

AF:

0.818

Gnomad4 NFE

AF:

0.834

Gnomad4 OTH

AF:

0.829

Alfa

AF:

0.831

Hom.:

69053

Bravo

AF:

0.808

Asia WGS

AF:

0.832

AC:

2893

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

3-methylcrotonyl-CoA carboxylase 2 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.1

DANN

Benign

0.66

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

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