rs16869487

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022132.5(MCCC2):​c.1150-944G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0947 in 152,098 control chromosomes in the GnomAD database, including 1,079 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.095 ( 1079 hom., cov: 32)

Consequence

MCCC2
NM_022132.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.945
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=-0.79).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MCCC2NM_022132.5 linkuse as main transcriptc.1150-944G>A intron_variant ENST00000340941.11 NP_071415.1
MCCC2NM_001363147.1 linkuse as main transcriptc.1036-944G>A intron_variant NP_001350076.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MCCC2ENST00000340941.11 linkuse as main transcriptc.1150-944G>A intron_variant 1 NM_022132.5 ENSP00000343657 P1Q9HCC0-1

Frequencies

GnomAD3 genomes
AF:
0.0945
AC:
14360
AN:
151980
Hom.:
1065
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.202
Gnomad AMI
AF:
0.0703
Gnomad AMR
AF:
0.0377
Gnomad ASJ
AF:
0.0305
Gnomad EAS
AF:
0.0859
Gnomad SAS
AF:
0.103
Gnomad FIN
AF:
0.0858
Gnomad MID
AF:
0.0538
Gnomad NFE
AF:
0.0480
Gnomad OTH
AF:
0.0681
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0947
AC:
14410
AN:
152098
Hom.:
1079
Cov.:
32
AF XY:
0.0952
AC XY:
7076
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.202
Gnomad4 AMR
AF:
0.0376
Gnomad4 ASJ
AF:
0.0305
Gnomad4 EAS
AF:
0.0861
Gnomad4 SAS
AF:
0.102
Gnomad4 FIN
AF:
0.0858
Gnomad4 NFE
AF:
0.0480
Gnomad4 OTH
AF:
0.0731
Alfa
AF:
0.0761
Hom.:
262
Bravo
AF:
0.0951
Asia WGS
AF:
0.130
AC:
451
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
11
DANN
Benign
0.85

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.

Other links and lift over

dbSNP: rs16869487; hg19: chr5-70941094; COSMIC: COSV60157160; COSMIC: COSV60157160; API