5-71587123-C-G

Position:

• chr5-71587123-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000682045.1(MCCC2):​c.-16+273C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,192 control chromosomes in the GnomAD database, including 47,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.78 (47350 hom., cov: 33)
• Consequence: MCCC2 ENST00000682045.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0360

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-71587123-C-G is Benign according to our data. Variant chr5-71587123-C-G is described in ClinVar as [Benign]. Clinvar id is 684213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCCC2	ENST00000682045.1	c.-16+273C>G		intron_variant
MCCC2	ENST00000682214.1	c.-198+273C>G		intron_variant
MCCC2	ENST00000505787.8	n.1969+2957C>G		intron_variant, non_coding_transcript_variant		5
MCCC2	ENST00000682499.1	n.950+4550C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119118 AN: 152074 Hom.: 47328 Cov.: 33

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.815

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.783 AC: 119198 AN: 152192 Hom.: 47350 Cov.: 33 AF XY: 0.786 AC XY: 58476 AN XY: 74426

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.811

Alfa AF: 0.794 Hom.: 5667

Bravo AF: 0.782

Asia WGS AF: 0.826 AC: 2873 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.37
DANN	Benign	0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13157835; hg19: chr5-70882950;