chr16-83915335-G-T

Variant names:

• chr16-83915335-G-T
• rs200278015
• NM_012213.3:c.1328G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_012213.3(MLYCD):​c.1328G>T​(p.Gly443Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G443A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MLYCD NM_012213.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.38
• 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_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.996

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012213.3. 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.1328G>T	p.Gly443Val	missense	Exon 5 of 5	NP_036345.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLYCD	ENST00000262430.6	TSL:1 MANE Select	c.1328G>T	p.Gly443Val	missense	Exon 5 of 5	ENSP00000262430.4
	MLYCD	ENST00000569024.1	TSL:6	n.3653G>T		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000288849	ENST00000689373.1		n.2001G>T		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.50
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.81	D
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.60	D
MetaRNN	Pathogenic	1.0	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		9.4
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-8.2	D
REVEL	Pathogenic	0.92
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.94		Loss of loop (P = 0.0804)
MVP		0.99
MPC		0.16
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.98
gMVP		0.88

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: rs200278015; hg19: chr16-83948940;