rs147617160

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012213.3(MLYCD):c.541G>A(p.Val181Met) variant causes a missense change. The variant allele was found at a frequency of 0.00034 in 1,614,024 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00072 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

MLYCD
NM_012213.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.37

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 links:

ENSG00000288849 (HGNC:):

ENSG00000288849 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017965019).

BP6

Variant 16-83906999-G-A is Benign according to our data. Variant chr16-83906999-G-A is described in ClinVar as [Benign]. Clinvar id is 460445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-83906999-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000716 (109/152298) while in subpopulation EAS AF= 0.0158 (82/5180). AF 95% confidence interval is 0.0131. There are 3 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLYCD	NM_012213.3 link	c.541G>A	p.Val181Met	missense_variant	Exon 2 of 5	ENST00000262430.6	NP_036345.2	O95822-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MLYCD	ENST00000262430.6 link	c.541G>A	p.Val181Met	missense_variant	Exon 2 of 5	1	NM_012213.3	ENSP00000262430.4	O95822-1
ENSG00000288849	ENST00000689373.1 link	n.1214G>A		non_coding_transcript_exon_variant	Exon 6 of 9
ENSG00000288849	ENST00000692462.1 link	n.1182G>A		non_coding_transcript_exon_variant	Exon 6 of 9

Frequencies

GnomAD3 genomes

AF:

0.000716

AC:

109

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00129

AC:

321

AN:

249584

Hom.:

AF XY:

0.00116

AC XY:

157

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0171

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000825

GnomAD4 exome

AF:

0.000300

AC:

439

AN:

1461726

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

188

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00844

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.000716

AC:

109

AN:

152298

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0158

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000458

Hom.:

Bravo

AF:

0.000623

ESP6500AA

AF:

0.000266

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00103

AC:

124

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deficiency of malonyl-CoA decarboxylase

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.018

MetaSVM

Uncertain

0.63

MutationAssessor

Uncertain

2.8

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.90

REVEL

Uncertain

0.48

Sift

Benign

0.15

Sift4G

Benign

0.21

Polyphen

1.0

Vest4

0.38

MVP

0.95

MPC

0.024

ClinPred

0.066

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.33

gMVP

0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over