Genetic Variant MLYCD:p.Gly3Val (chr16-83899152-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2PM5BP4

The NM_012213.3(MLYCD):c.8G>T(p.Gly3Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G3D) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MLYCD
NM_012213.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50

Publications

2 publications found

Variant links:

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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, PanelApp Australia, G2P

MLYCD links:

ENSG00000288849 (HGNC:):

ENSG00000288849 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr16-83899152-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 4059.

BP4

Computational evidence support a benign effect (MetaRNN=0.28410923).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLYCD	NM_012213.3	MANE Select	c.8G>T	p.Gly3Val	missense	Exon 1 of 5	NP_036345.2	O95822-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MLYCD	ENST00000262430.6	TSL:1 MANE Select	c.8G>T	p.Gly3Val	missense	Exon 1 of 5	ENSP00000262430.4	O95822-1
MLYCD	ENST00000851351.1		c.8G>T	p.Gly3Val	missense	Exon 1 of 5	ENSP00000521410.1
MLYCD	ENST00000851350.1		c.8G>T	p.Gly3Val	missense	Exon 1 of 4	ENSP00000521409.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

996192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

475714

African (AFR)

AF:

0.00

AC:

AN:

19440

American (AMR)

AF:

0.00

AC:

AN:

6086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10140

East Asian (EAS)

AF:

0.00

AC:

AN:

14452

South Asian (SAS)

AF:

0.00

AC:

AN:

23020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15124

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2450

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

868792

Other (OTH)

AF:

0.00

AC:

AN:

36688

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Deficiency of malonyl-CoA decarboxylase (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.13

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.64

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.46

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.35

MutationAssessor

Benign

0.97

PhyloP100

1.5

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.74

REVEL

Benign

0.22

Sift

Benign

0.35

Sift4G

Benign

0.38

Polyphen

0.0020

Vest4

0.29

MutPred

0.39

Gain of sheet (P = 0.0125)

MVP

0.95

MPC

1.5

ClinPred

0.25

GERP RS

3.4

PromoterAI

0.097

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.16

gMVP

0.46

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over