3-183017029-A-G

Variant names:

• chr3-183017029-A-G
• rs537365135
• NM_020166.5:c.2049+237T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_020166.5(MCCC1):​c.2049+237T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 553,938 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00044 (0 hom.)
• Consequence: MCCC1 NM_020166.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18
• Publications: 0 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-AS1 (HGNC:40366): (MCCC1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-183017029-A-G is Benign according to our data. Variant chr3-183017029-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1190917.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00388 (591/152374) while in subpopulation AFR AF = 0.0133 (555/41590). AF 95% confidence interval is 0.0124. There are 2 homozygotes in GnomAd4. There are 268 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020166.5. 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
	MCCC1	NM_020166.5	MANE Select	c.2049+237T>C		intron	N/A	NP_064551.3
	MCCC1	NM_001363880.1		c.1722+237T>C		intron	N/A	NP_001350809.1	E9PHF7
	MCCC1	NM_001293273.2		c.1698+237T>C		intron	N/A	NP_001280202.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCCC1	ENST00000265594.9	TSL:1 MANE Select	c.2049+237T>C		intron	N/A	ENSP00000265594.4	Q96RQ3
	MCCC1	ENST00000492597.5	TSL:1	c.1722+237T>C		intron	N/A	ENSP00000419898.1	E9PHF7
	MCCC1	ENST00000497830.5	TSL:1	n.*1646+237T>C		intron	N/A	ENSP00000420088.1	F2Z3E2

Frequencies

GnomAD3 genomes AF: 0.00387 AC: 589 AN: 152256 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.000438 AC: 176 AN: 401564 Hom.: 0 Cov.: 2 AF XY: 0.000347 AC XY: 74 AN XY: 213362

African (AFR) AF: 0.0119 AC: 136 AN: 11386

American (AMR) AF: 0.000927 AC: 16 AN: 17256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12246

East Asian (EAS) AF: 0.00 AC: 0 AN: 26422

South Asian (SAS) AF: 0.00 AC: 0 AN: 43910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23812

Middle Eastern (MID) AF: 0.000582 AC: 1 AN: 1718

European-Non Finnish (NFE) AF: 0.0000372 AC: 9 AN: 241634

Other (OTH) AF: 0.000604 AC: 14 AN: 23180

GnomAD4 genome AF: 0.00388 AC: 591 AN: 152374 Hom.: 2 Cov.: 33 AF XY: 0.00360 AC XY: 268 AN XY: 74524

African (AFR) AF: 0.0133 AC: 555 AN: 41590

American (AMR) AF: 0.00170 AC: 26 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68038

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00264 Hom.: 0

Bravo AF: 0.00446

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		1.2

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

Other links and lift over

dbSNP: rs537365135; hg19: chr3-182734817;