chr3-183113900-C-T

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCCC1	XM_047448586.1	c.38+1574G>A		intron_variant	Intron 1 of 18		XP_047304542.1
MCCC1	XM_047448591.1	c.38+1574G>A		intron_variant	Intron 1 of 12		XP_047304547.1
LOC105374247	XR_924772.3	n.263-97C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCCC1	ENST00000492597.5	c.-102+1574G>A		intron_variant	Intron 1 of 17	1		ENSP00000419898.1
ENSG00000305074	ENST00000808387.1	n.244-97C>T		intron_variant	Intron 1 of 1

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 v4.3

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;