16-83932831-C-T

Position:

• chr16-83932831-C-T

Variant summary

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

The ENST00000561562.5(MLYCD):​c.302-16572C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,232 control chromosomes in the GnomAD database, including 3,690 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 0.21 (3689 hom., cov: 33)
  • Exomes 𝑓: 0.22 (1 hom.)
• Consequence: MLYCD ENST00000561562.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.544

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 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.302-16572C>T		intron_variant		2		ENSP00000484042
OSGIN1	ENST00000563248.2	n.660C>T		non_coding_transcript_exon_variant	2/2	3
MLYCD	ENST00000563312.5	c.259-16206C>T		intron_variant, NMD_transcript_variant		2		ENSP00000477143

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32612 AN: 152028 Hom.: 3690 Cov.: 33

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.206

GnomAD4 exome AF: 0.221 AC: 19 AN: 86 Hom.: 1 Cov.: 0 AF XY: 0.227 AC XY: 15 AN XY: 66

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.214 AC: 32623 AN: 152146 Hom.: 3689 Cov.: 33 AF XY: 0.218 AC XY: 16195 AN XY: 74396

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.208

Alfa AF: 0.141 Hom.: 334

Bravo AF: 0.213

Asia WGS AF: 0.270 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.76

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: rs12051537; hg19: chr16-83966436;