chr16-83915471-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012213.3(MLYCD):c.1464A>G(p.Gln488Gln) variant causes a synonymous change. The variant allele was found at a frequency of 0.00205 in 1,612,274 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 13 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 26 hom. )

Consequence

MLYCD
NM_012213.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.81

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

MLYCD links:

ENSG00000288849 (HGNC:):

ENSG00000288849 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 16-83915471-A-G is Benign according to our data. Variant chr16-83915471-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 320740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00807 (1229/152350) while in subpopulation AFR AF = 0.0268 (1112/41570). AF 95% confidence interval is 0.0254. There are 13 homozygotes in GnomAd4. There are 587 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLYCD	NM_012213.3 link	c.1464A>G	p.Gln488Gln	synonymous_variant	Exon 5 of 5	ENST00000262430.6	NP_036345.2	O95822-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLYCD	ENST00000262430.6 link	c.1464A>G	p.Gln488Gln	synonymous_variant	Exon 5 of 5	1	NM_012213.3	ENSP00000262430.4		O95822-1

Frequencies

GnomAD3 genomes

AF:

0.00806

AC:

1227

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0268

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00717

GnomAD2 exomes

AF:

0.00241

AC:

588

AN:

243998

AF XY:

0.00191

show subpopulations

Gnomad AFR exome

AF:

0.0271

Gnomad AMR exome

AF:

0.00264

Gnomad ASJ exome

AF:

0.00121

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000628

Gnomad OTH exome

AF:

0.00284

GnomAD4 exome

AF:

0.00142

AC:

2078

AN:

1459924

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

979

AN XY:

726302

show subpopulations

African (AFR)

AF:

0.0303

AC:

1013

AN:

33474

American (AMR)

AF:

0.00273

AC:

122

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000765

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51536

Middle Eastern (MID)

AF:

0.00539

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000631

AC:

702

AN:

1111978

Other (OTH)

AF:

0.00310

AC:

187

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

140

280

421

561

701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00807

AC:

1229

AN:

152350

Hom.:

Cov.:

AF XY:

0.00788

AC XY:

587

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.0268

AC:

1112

AN:

41570

American (AMR)

AF:

0.00379

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000588

AC:

AN:

68034

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

114

170

227

284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00351

Hom.:

Bravo

AF:

0.00913

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000830

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deficiency of malonyl-CoA decarboxylase

Benign:3

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 16, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not specified

Benign:1

Apr 06, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.9

(source)

DANN

Benign

0.65

PhyloP100

3.8

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over