chr16-83908260-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012213.3(MLYCD):c.776G>C(p.Gly259Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,614,142 control chromosomes in the GnomAD database, including 234 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G259S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0039 ( 32 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 202 hom. )

Consequence

MLYCD
NM_012213.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.22

Publications

4 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, G2P, Orphanet

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 (MetaRNN=0.002562791).

BP6

Variant 16-83908260-G-C is Benign according to our data. Variant chr16-83908260-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 95505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.095 is higher than 0.05.

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.776G>C	p.Gly259Ala	missense	Exon 3 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.776G>C	p.Gly259Ala	missense	Exon 3 of 5	ENSP00000262430.4	O95822-1
MLYCD	ENST00000851351.1		c.803G>C	p.Gly268Ala	missense	Exon 3 of 5	ENSP00000521410.1
MLYCD	ENST00000851350.1		c.776G>C	p.Gly259Ala	missense	Exon 3 of 4	ENSP00000521409.1

Frequencies

GnomAD3 genomes

AF:

0.00390

AC:

593

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00755

AC:

1884

AN:

249554

AF XY:

0.00700

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.000894

Gnomad EAS exome

AF:

0.0987

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00330

GnomAD4 exome

AF:

0.00302

AC:

4411

AN:

1461858

Hom.:

202

Cov.:

AF XY:

0.00304

AC XY:

2214

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33476

American (AMR)

AF:

0.000134

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000957

AC:

AN:

26136

East Asian (EAS)

AF:

0.0970

AC:

3850

AN:

39700

South Asian (SAS)

AF:

0.00234

AC:

202

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000665

AC:

AN:

1112004

Other (OTH)

AF:

0.00401

AC:

242

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

237

474

710

947

1184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.00386

AC:

588

AN:

152284

Hom.:

Cov.:

AF XY:

0.00428

AC XY:

319

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.000433

AC:

AN:

41558

American (AMR)

AF:

0.000392

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.102

AC:

529

AN:

5178

South Asian (SAS)

AF:

0.00373

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68026

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

123

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:

0.00297

Hom.:

Bravo

AF:

0.00476

ESP6500AA

AF:

0.000514

AC:

ESP6500EA

AF:

0.000243

AC:

ExAC

AF:

0.00729

AC:

881

Asia WGS

AF:

0.0300

AC:

103

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Deficiency of malonyl-CoA decarboxylase (2)

not specified (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.37

CADD

Benign

1.5

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.078

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.64

PhyloP100

1.2

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.39

REVEL

Benign

0.084

Sift

Benign

0.39

Sift4G

Benign

0.67

Polyphen

0.013

Vest4

0.18

MVP

0.87

MPC

0.019

ClinPred

0.00052

GERP RS

0.49

PromoterAI

-0.0090

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.21

Mutation Taster

=93/7

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over