chr16-83932831-C-T

Variant names:

• chr16-83932831-C-T
• rs12051537
• ENST00000561562.5:c.301-16572C>T

Variant summary

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

The ENST00000561562.5(MLYCD):​c.301-16572C>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
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLYCD	ENST00000561562.5	TSL:2	c.301-16572C>T		intron	N/A	ENSP00000484042.1
	OSGIN1	ENST00000563248.2	TSL:3	n.660C>T		non_coding_transcript_exon	Exon 2 of 2
	MLYCD	ENST00000563312.5	TSL:2	n.259-16206C>T		intron	N/A	ENSP00000477143.1

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.230 AC: 17 AN: 74

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.214 AC: 8872 AN: 41478

American (AMR) AF: 0.224 AC: 3427 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 578 AN: 3470

East Asian (EAS) AF: 0.345 AC: 1781 AN: 5166

South Asian (SAS) AF: 0.153 AC: 739 AN: 4824

European-Finnish (FIN) AF: 0.299 AC: 3169 AN: 10602

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13404 AN: 67994

Other (OTH) AF: 0.208 AC: 440 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.76
PhyloP100		0.54

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: rs12051537; hg19: chr16-83966436;