16-83907796-A-G

Variant names:

• chr16-83907796-A-G
• rs11649200
• NM_012213.3:c.642-330A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012213.3(MLYCD):​c.642-330A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,062 control chromosomes in the GnomAD database, including 4,747 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4747 hom., cov: 32)
• Consequence: MLYCD NM_012213.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 8 publications found

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

ENSG00000288849 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLYCD	NM_012213.3	MANE Select	c.642-330A>G		intron	N/A	NP_036345.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLYCD	ENST00000262430.6	TSL:1 MANE Select	c.642-330A>G		intron	N/A	ENSP00000262430.4
	ENSG00000288849	ENST00000689373.1		n.1315-330A>G		intron	N/A
	ENSG00000288849	ENST00000692462.1		n.1283-330A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34505 AN: 151944 Hom.: 4722 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.195

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.227 AC: 34586 AN: 152062 Hom.: 4747 Cov.: 32 AF XY: 0.224 AC XY: 16669 AN XY: 74330

African (AFR) AF: 0.388 AC: 16062 AN: 41426

American (AMR) AF: 0.200 AC: 3047 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3470

East Asian (EAS) AF: 0.240 AC: 1241 AN: 5164

South Asian (SAS) AF: 0.158 AC: 760 AN: 4812

European-Finnish (FIN) AF: 0.122 AC: 1296 AN: 10614

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.160 AC: 10895 AN: 67986

Other (OTH) AF: 0.193 AC: 409 AN: 2116

Alfa AF: 0.181 Hom.: 10803

Bravo AF: 0.242

Asia WGS AF: 0.229 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.11
DANN	Benign	0.20
PhyloP100		-1.6
PromoterAI		-0.018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11649200; hg19: chr16-83941401;