ENST00000561562.5:c.301-1758G>A

Variant names:

• chr16-83910609-G-A
• rs1188388264
• NM_012213.3:c.799-1609G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000561562.5(MLYCD):​c.151-1609G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 151,238 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000060 (0 hom., cov: 28)
• Consequence: MLYCD ENST00000561562.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89
• Publications: 0 publications found

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]

MLYCD Gene-Disease associations (from GenCC):

• malonic aciduria

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet, PanelApp Australia

ENSG00000288849 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000561562.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLYCD	NM_012213.3	MANE Select	c.799-1609G>A		intron	N/A	NP_036345.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLYCD	ENST00000262430.6	TSL:1 MANE Select	c.799-1609G>A		intron	N/A	ENSP00000262430.4
	MLYCD	ENST00000561562.5	TSL:2	c.151-1609G>A		intron	N/A	ENSP00000484042.1
	MLYCD	ENST00000563312.5	TSL:2	n.109-1609G>A		intron	N/A	ENSP00000477143.1

Frequencies

GnomAD3 genomes AF: 0.0000595 AC: 9 AN: 151238 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000729

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000737

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000595 AC: 9 AN: 151238 Hom.: 0 Cov.: 28 AF XY: 0.0000407 AC XY: 3 AN XY: 73760

African (AFR) AF: 0.0000729 AC: 3 AN: 41132

American (AMR) AF: 0.00 AC: 0 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5102

South Asian (SAS) AF: 0.00 AC: 0 AN: 4770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000737 AC: 5 AN: 67882

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.0000907

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.88
DANN	Benign	0.60
PhyloP100		-2.9

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: rs1188388264; hg19: chr16-83944214;