rs12637471

Variant names:

• chr3-183044649-G-A
• rs12637471
• NM_020166.5:c.1083+764C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-183044649-G-A
• chr3-183044649-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020166.5(MCCC1):​c.1083+764C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,978 control chromosomes in the GnomAD database, including 5,225 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 0.25 (5225 hom., cov: 31)
• Consequence: MCCC1 NM_020166.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950

Genes affected

MCCC1 (HGNC:6936): (methylcrotonyl-CoA carboxylase subunit 1) This gene encodes the large 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCCC1	NM_020166.5	c.1083+764C>T		intron_variant	Intron 10 of 18	ENST00000265594.9	NP_064551.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCCC1	ENST00000265594.9	c.1083+764C>T		intron_variant	Intron 10 of 18	1	NM_020166.5	ENSP00000265594.4

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37478 AN: 151860 Hom.: 5209 Cov.: 31

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.247 AC: 37536 AN: 151978 Hom.: 5225 Cov.: 31 AF XY: 0.252 AC XY: 18711 AN XY: 74266

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.231

Alfa AF: 0.175 Hom.: 808

Bravo AF: 0.260

Asia WGS AF: 0.417 AC: 1449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs12637471; hg19: chr3-182762437; COSMIC: COSV55608442;