Variant chr5-71652791-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022132.5(MCCC2):c.1574+37C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,550,190 control chromosomes in the GnomAD database, including 236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 23 hom., cov: 33)

Exomes 𝑓: 0.015 ( 213 hom. )

Consequence

MCCC2
NM_022132.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.14

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=-0.88).

BP6

Variant 5-71652791-C-G is Benign according to our data. Variant chr5-71652791-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 261557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0118 (1801/152338) while in subpopulation NFE AF= 0.016 (1090/68034). AF 95% confidence interval is 0.0152. There are 23 homozygotes in gnomad4. There are 909 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCCC2	NM_022132.5 link	c.1574+37C>G		intron_variant		ENST00000340941.11	NP_071415.1	Q9HCC0-1A0A140VK29
MCCC2	NM_001363147.1 link	c.1460+37C>G		intron_variant			NP_001350076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCCC2	ENST00000340941.11 link	c.1574+37C>G		intron_variant		1	NM_022132.5	ENSP00000343657.6		Q9HCC0-1

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1803

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00968

Gnomad ASJ

AF:

0.0207

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0350

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0160

Gnomad OTH

AF:

0.00957

GnomAD3 exomes

AF:

0.0122

AC:

3068

AN:

250460

Hom.:

AF XY:

0.0117

AC XY:

1579

AN XY:

135422

show subpopulations

Gnomad AFR exome

AF:

0.00261

Gnomad AMR exome

AF:

0.00737

Gnomad ASJ exome

AF:

0.0181

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000491

Gnomad FIN exome

AF:

0.0341

Gnomad NFE exome

AF:

0.0155

Gnomad OTH exome

AF:

0.0136

GnomAD4 exome

AF:

0.0147

AC:

20493

AN:

1397852

Hom.:

213

Cov.:

AF XY:

0.0142

AC XY:

9914

AN XY:

699424

show subpopulations

Gnomad4 AFR exome

AF:

0.00231

Gnomad4 AMR exome

AF:

0.00744

Gnomad4 ASJ exome

AF:

0.0194

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000695

Gnomad4 FIN exome

AF:

0.0309

Gnomad4 NFE exome

AF:

0.0162

Gnomad4 OTH exome

AF:

0.0114

GnomAD4 genome

AF:

0.0118

AC:

1801

AN:

152338

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

909

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00967

Gnomad4 ASJ

AF:

0.0207

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0350

Gnomad4 NFE

AF:

0.0160

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.00955

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 01, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.52

DANN

Benign

0.41

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