5-71587242-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The ENST00000682045.1(MCCC2):​c.-16+392G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,051,144 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 8 hom., cov: 34)
Exomes 𝑓: 0.00051 ( 6 hom. )

Consequence

MCCC2
ENST00000682045.1 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.03
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
Variant 5-71587242-G-A is Benign according to our data. Variant chr5-71587242-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1213286.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00466 (710/152362) while in subpopulation AFR AF= 0.0165 (686/41596). AF 95% confidence interval is 0.0155. There are 8 homozygotes in gnomad4. There are 334 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MCCC2ENST00000682045.1 linkuse as main transcriptc.-16+392G>A intron_variant
MCCC2ENST00000682214.1 linkuse as main transcriptc.-198+392G>A intron_variant
MCCC2ENST00000505787.8 linkuse as main transcriptn.1969+3076G>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00462
AC:
703
AN:
152242
Hom.:
8
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0164
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00105
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00192
GnomAD4 exome
AF:
0.000512
AC:
460
AN:
898782
Hom.:
6
Cov.:
12
AF XY:
0.000462
AC XY:
206
AN XY:
445484
show subpopulations
Gnomad4 AFR exome
AF:
0.0199
Gnomad4 AMR exome
AF:
0.000709
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000207
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000116
Gnomad4 OTH exome
AF:
0.00126
GnomAD4 genome
AF:
0.00466
AC:
710
AN:
152362
Hom.:
8
Cov.:
34
AF XY:
0.00448
AC XY:
334
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.0165
Gnomad4 AMR
AF:
0.00105
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00319
Hom.:
2
Bravo
AF:
0.00531
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxApr 09, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
CADD
Benign
18
DANN
Benign
0.95

Splicing

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.

Other links and lift over

dbSNP: rs140854474; hg19: chr5-70883069; API