5-71587090-A-T

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+240A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,116 control chromosomes in the GnomAD database, including 15,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.44 (15451 hom., cov: 33)
• Consequence: MCCC2 ENST00000682045.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.175

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 5-71587090-A-T is Benign according to our data. Variant chr5-71587090-A-T is described in ClinVar as [Benign]. Clinvar id is 684211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.53 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+240A>T		intron_variant
MCCC2	ENST00000682214.1	c.-198+240A>T		intron_variant
MCCC2	ENST00000505787.8	n.1969+2924A>T		intron_variant, non_coding_transcript_variant		5
MCCC2	ENST00000682499.1	n.950+4517A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67635 AN: 151998 Hom.: 15450 Cov.: 33

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.445 AC: 67664 AN: 152116 Hom.: 15451 Cov.: 33 AF XY: 0.447 AC XY: 33238 AN XY: 74360

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.447

Alfa AF: 0.456 Hom.: 1988

Bravo AF: 0.424

Asia WGS AF: 0.445 AC: 1547 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	1.1
Dann	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs467413; hg19: chr5-70882917; COSMIC: COSV60153010;