rs2245222

Positions:

• chr16-83947645-G-A
• chr16-83947645-G-C
• chr16-83947645-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000561562.5(MLYCD):​c.302-1758G>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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLYCD	ENST00000561562.5	c.302-1758G>A		intron_variant		2		ENSP00000484042
MLYCD	ENST00000563312.5	c.259-1392G>A		intron_variant, NMD_transcript_variant		2		ENSP00000477143
MLYCD	ENST00000566309.2	c.259-566G>A		intron_variant, NMD_transcript_variant		2		ENSP00000476300
OSGIN1	ENST00000566667.2	n.109-566G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.273

Alfa AF: 0.184 Hom.: 3084

Bravo AF: 0.329

Asia WGS AF: 0.193 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs2245222; hg19: chr16-83981250;