ENST00000492597.5:c.-102+1574G>A

Variant names:

• chr3-183113900-C-T
• rs11716740
• ENST00000492597.5:c.-102+1574G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000492597.5(MCCC1):​c.-102+1574G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 151,888 control chromosomes in the GnomAD database, including 1,070 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 0.11 (1070 hom., cov: 31)
• Consequence: MCCC1 ENST00000492597.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 6 publications found

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]

MCCC1 Gene-Disease associations (from GenCC):

• 3-methylcrotonyl-CoA carboxylase 1 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 3-methylcrotonyl-CoA carboxylase deficiency

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ENSG00000305074 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000492597.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCCC1	ENST00000492597.5	TSL:1	c.-102+1574G>A		intron	N/A	ENSP00000419898.1
	ENSG00000305074	ENST00000808387.1		n.244-97C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16772 AN: 151770 Hom.: 1069 Cov.: 31

Gnomad AFR AF: 0.0588

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0905

Gnomad ASJ AF: 0.0920

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.110 AC: 16774 AN: 151888 Hom.: 1070 Cov.: 31 AF XY: 0.110 AC XY: 8148 AN XY: 74238

African (AFR) AF: 0.0587 AC: 2432 AN: 41418

American (AMR) AF: 0.0904 AC: 1379 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0920 AC: 319 AN: 3466

East Asian (EAS) AF: 0.173 AC: 895 AN: 5164

South Asian (SAS) AF: 0.146 AC: 699 AN: 4790

European-Finnish (FIN) AF: 0.116 AC: 1226 AN: 10554

Middle Eastern (MID) AF: 0.172 AC: 50 AN: 290

European-Non Finnish (NFE) AF: 0.138 AC: 9405 AN: 67936

Other (OTH) AF: 0.118 AC: 249 AN: 2104

Alfa AF: 0.131 Hom.: 2513

Bravo AF: 0.105

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.4
DANN	Benign	0.23
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11716740; hg19: chr3-182831688;