16-83906999-G-T

Variant names:

• chr16-83906999-G-T
• NM_012213.3:c.541G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012213.3(MLYCD):​c.541G>T​(p.Val181Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V181M) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MLYCD NM_012213.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.37

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]

ENSG00000288849 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLYCD	NM_012213.3	c.541G>T	p.Val181Leu	missense_variant	Exon 2 of 5	ENST00000262430.6	NP_036345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLYCD	ENST00000262430.6	c.541G>T	p.Val181Leu	missense_variant	Exon 2 of 5	1	NM_012213.3	ENSP00000262430.4
ENSG00000288849	ENST00000689373.1	n.1214G>T		non_coding_transcript_exon_variant	Exon 6 of 9
ENSG00000288849	ENST00000692462.1	n.1182G>T		non_coding_transcript_exon_variant	Exon 6 of 9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461728 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727184

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.41
Sift	Benign	0.51	T
Sift4G	Benign	0.64	T
Polyphen		0.75	P
Vest4		0.51
MutPred		0.64		Loss of catalytic residue at V181 (P = 0.0424);
MVP		0.93
MPC		0.020
ClinPred		0.57	D
GERP RS		5.2
Varity_R		0.53
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-83940604;