dbSNP rs937652: MCCC1:c.-101-4935G>C (chr3-183099540-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001363880.1(MCCC1):c.-290G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,429,106 control chromosomes in the GnomAD database, including 413,985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 32632 hom., cov: 34)

Exomes 𝑓: 0.77 ( 381353 hom. )

Consequence

MCCC1
NM_001363880.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.31

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 3-183099540-C-G is Benign according to our data. Variant chr3-183099540-C-G is described in ClinVar as [Benign]. Clinvar id is 344318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCCC1	NM_020166.5 link	c.-100G>C		upstream_gene_variant		ENST00000265594.9	NP_064551.3	Q96RQ3A0A0S2Z693

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCCC1	ENST00000265594.9 link	c.-100G>C		upstream_gene_variant		1	NM_020166.5	ENSP00000265594.4		Q96RQ3

Frequencies

GnomAD3 genomes

AF:

0.611

AC:

92915

AN:

152114

Hom.:

32651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.818

Gnomad AMR

AF:

0.550

Gnomad ASJ

AF:

0.723

Gnomad EAS

AF:

0.649

Gnomad SAS

AF:

0.775

Gnomad FIN

AF:

0.795

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.791

Gnomad OTH

AF:

0.644

GnomAD4 exome

AF:

0.766

AC:

978651

AN:

1276874

Hom.:

381353

Cov.:

AF XY:

0.769

AC XY:

486727

AN XY:

633204

show subpopulations

Gnomad4 AFR exome

AF:

0.238

Gnomad4 AMR exome

AF:

0.508

Gnomad4 ASJ exome

AF:

0.724

Gnomad4 EAS exome

AF:

0.647

Gnomad4 SAS exome

AF:

0.777

Gnomad4 FIN exome

AF:

0.787

Gnomad4 NFE exome

AF:

0.798

Gnomad4 OTH exome

AF:

0.727

GnomAD4 genome

AF:

0.610

AC:

92898

AN:

152232

Hom.:

32632

Cov.:

AF XY:

0.611

AC XY:

45449

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.250

Gnomad4 AMR

AF:

0.549

Gnomad4 ASJ

AF:

0.723

Gnomad4 EAS

AF:

0.649

Gnomad4 SAS

AF:

0.774

Gnomad4 FIN

AF:

0.795

Gnomad4 NFE

AF:

0.791

Gnomad4 OTH

AF:

0.640

Alfa

AF:

0.699

Hom.:

5040

Bravo

AF:

0.575

Asia WGS

AF:

0.642

AC:

2234

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Methylcrotonyl-CoA carboxylase deficiency

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

3-methylcrotonyl-CoA carboxylase 1 deficiency

Benign:1

Jun 15, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

3.0

DANN

Benign

0.79

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over