rs62640904

chr16-83899588-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_012213.3(MLYCD):c.444C>T(p.Asp148=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,589,408 control chromosomes in the GnomAD database, including 435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (198 hom., cov: 33)
  • Exomes 𝑓: 0.010 (237 hom.)
• Consequence: MLYCD NM_012213.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.805

Genes affected

MLYCD (HGNC:7150): (malonyl-CoA decarboxylase) The product of this gene catalyzes the breakdown of malonyl-CoA to acetyl-CoA and carbon dioxide. Malonyl-CoA is an intermediate in fatty acid biosynthesis, and also inhibits the transport of fatty acyl CoAs into mitochondria. Consequently, the encoded protein acts to increase the rate of fatty acid oxidation. It is found in mitochondria, peroxisomes, and the cytoplasm. Mutations in this gene result in malonyl-CoA decarboyxlase deficiency. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 16-83899588-C-T is Benign according to our data. Variant chr16-83899588-C-T is described in ClinVar as [Benign]. Clinvar id is 95500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-83899588-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.805 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.093 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLYCD	NM_012213.3	c.444C>T	p.Asp148=	synonymous_variant	1/5	ENST00000262430.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLYCD	ENST00000262430.6	c.444C>T	p.Asp148=	synonymous_variant	1/5	1	NM_012213.3	P1

Frequencies

GnomAD3 genomes AF: 0.0331 AC: 5043 AN: 152198 Hom.: 196 Cov.: 33

Gnomad AFR AF: 0.0951

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00970

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00913

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.0132 AC: 2678 AN: 202962 Hom.: 62 AF XY: 0.0121 AC XY: 1368 AN XY: 113526

Gnomad AFR exome AF: 0.0979

Gnomad AMR exome AF: 0.00666

Gnomad ASJ exome AF: 0.0196

Gnomad EAS exome AF: 0.000124

Gnomad SAS exome AF: 0.00171

Gnomad FIN exome AF: 0.0141

Gnomad NFE exome AF: 0.0105

Gnomad OTH exome AF: 0.0120

GnomAD4 exome AF: 0.0104 AC: 14934 AN: 1437094 Hom.: 237 Cov.: 30 AF XY: 0.0100 AC XY: 7161 AN XY: 714780

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.00866

Gnomad4 ASJ exome AF: 0.0206

Gnomad4 EAS exome AF: 0.000205

Gnomad4 SAS exome AF: 0.00193

Gnomad4 FIN exome AF: 0.0125

Gnomad4 NFE exome AF: 0.00826

Gnomad4 OTH exome AF: 0.0144

GnomAD4 genome AF: 0.0333 AC: 5070 AN: 152314 Hom.: 198 Cov.: 33 AF XY: 0.0319 AC XY: 2373 AN XY: 74478

Gnomad4 AFR AF: 0.0955

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00970

Gnomad4 NFE AF: 0.00913

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0202 Hom.: 25

Bravo AF: 0.0370

Asia WGS AF: 0.00866 AC: 32 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Deficiency of malonyl-CoA decarboxylase Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 31, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 28, 2012	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
Cadd	Benign	12
Dann	Benign	0.96

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: rs62640904; hg19: chr16-83933193;