16-83947645-G-A

Variant names:

• chr16-83947645-G-A
• rs2245222
• ENST00000561562.5:c.301-1758G>A

Variant summary

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

The ENST00000561562.5(MLYCD):​c.301-1758G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,154 control chromosomes in the GnomAD database, including 10,301 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 0.30 (10301 hom., cov: 34)
• Consequence: MLYCD ENST00000561562.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 6 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]

OSGIN1 (HGNC:30093): (oxidative stress induced growth inhibitor 1) This gene encodes an oxidative stress response protein that regulates cell death. Expression of the gene is regulated by p53 and is induced by DNA damage. The protein regulates apoptosis by inducing cytochrome c release from mitochondria. It also appears to be a key regulator of both inflammatory and anti-inflammatory molecules. The loss of this protein correlates with uncontrolled cell growth and tumor formation. Naturally occurring read-through transcription exists between this gene and the neighboring upstream malonyl-CoA decarboxylase (MLYCD) gene, but the read-through transcripts are unlikely to produce a protein product. [provided by RefSeq, Aug 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000561562.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLYCD	ENST00000561562.5	TSL:2	c.301-1758G>A		intron	N/A	ENSP00000484042.1
	MLYCD	ENST00000563312.5	TSL:2	n.259-1392G>A		intron	N/A	ENSP00000477143.1
	MLYCD	ENST00000566309.2	TSL:2	n.259-566G>A		intron	N/A	ENSP00000476300.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46122 AN: 152036 Hom.: 10258 Cov.: 34

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.304 AC: 46231 AN: 152154 Hom.: 10301 Cov.: 34 AF XY: 0.298 AC XY: 22183 AN XY: 74402

African (AFR) AF: 0.631 AC: 26188 AN: 41480

American (AMR) AF: 0.266 AC: 4074 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 750 AN: 3472

East Asian (EAS) AF: 0.139 AC: 716 AN: 5166

South Asian (SAS) AF: 0.189 AC: 910 AN: 4820

European-Finnish (FIN) AF: 0.125 AC: 1322 AN: 10614

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11479 AN: 67996

Other (OTH) AF: 0.273 AC: 577 AN: 2114

Alfa AF: 0.208 Hom.: 5673

Bravo AF: 0.329

Asia WGS AF: 0.193 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.45
DANN	Benign	0.70
PhyloP100		-1.4

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: rs2245222; hg19: chr16-83981250;