rs62640904

Variant names:

• chr16-83899588-C-G
• NM_012213.3:c.444C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-83899588-C-G
• chr16-83899588-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012213.3(MLYCD):​c.444C>G​(p.Asp148Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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. D148G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MLYCD NM_012213.3 missense
• Clinical Significance: Not reported in ClinVar
• 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]

ENSG00000288849 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29831362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLYCD	NM_012213.3	c.444C>G	p.Asp148Glu	missense_variant	Exon 1 of 5	ENST00000262430.6	NP_036345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLYCD	ENST00000262430.6	c.444C>G	p.Asp148Glu	missense_variant	Exon 1 of 5	1	NM_012213.3	ENSP00000262430.4
ENSG00000288849	ENST00000689373.1	n.1202-7399C>G		intron_variant	Intron 5 of 8
ENSG00000288849	ENST00000692462.1	n.1170-7399C>G		intron_variant	Intron 5 of 8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1437136 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 714802

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: 9.02e-7

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	0.096
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	17
DANN	Benign	0.84
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.69	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	-0.18	N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.68	N
REVEL	Uncertain	0.33
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.49		Loss of loop (P = 0.0804);
MVP		0.80
MPC		0.018
ClinPred		0.28	T
GERP RS		2.6
Varity_R		0.35
gMVP		0.097

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: chr16-83933193;