rs147617160

chr16-83906999-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.37

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]

ACMG classification

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 GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLYCD	NM_012213.3	c.541G>A	p.Val181Met	missense_variant	2/5	ENST00000262430.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLYCD	ENST00000262430.6	c.541G>A	p.Val181Met	missense_variant	2/5	1	NM_012213.3	P1

Frequencies

GnomAD3 genomes AF: 0.000716 AC: 109 AN: 152180 Hom.: 3 Cov.: 33

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.: 1 AF XY: 0.00116 AC XY: 157 AN XY: 135406

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.: 2 Cov.: 31 AF XY: 0.000259 AC XY: 188 AN XY: 727184

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.: 3 Cov.: 33 AF XY: 0.000685 AC XY: 51 AN XY: 74460

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.: 0

Bravo AF: 0.000623

ESP6500AA AF: 0.000266 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00103 AC: 124

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Deficiency of malonyl-CoA decarboxylase Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Uncertain	-0.070
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.018	T
MetaSVM	Uncertain	0.63	D
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.90	N
REVEL	Uncertain	0.48
Sift	Benign	0.15	T
Sift4G	Benign	0.21	T
Polyphen		1.0	D
Vest4		0.38
MVP		0.95
MPC		0.024
ClinPred		0.066	T
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

Other links and lift over

dbSNP: rs147617160; hg19: chr16-83940604;