rs561775245

chr16-83899411-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS1

The NM_012213.3(MLYCD):c.267C>T(p.Gly89=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,516,124 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (2 hom.)
• Consequence: MLYCD NM_012213.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.12

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 16-83899411-C-T is Benign according to our data. Variant chr16-83899411-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 460444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.12 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000162 (221/1364012) while in subpopulation SAS AF= 0.00244 (189/77308). AF 95% confidence interval is 0.00216. There are 2 homozygotes in gnomad4_exome. There are 144 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLYCD	NM_012213.3	c.267C>T	p.Gly89=	synonymous_variant	1/5	ENST00000262430.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLYCD	ENST00000262430.6	c.267C>T	p.Gly89=	synonymous_variant	1/5	1	NM_012213.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 152004 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000564 AC: 64 AN: 113490 Hom.: 0 AF XY: 0.000606 AC XY: 39 AN XY: 64350

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000196

Gnomad ASJ exome AF: 0.000145

Gnomad EAS exome AF: 0.000149

Gnomad SAS exome AF: 0.00277

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000213

Gnomad OTH exome AF: 0.000323

GnomAD4 exome AF: 0.000162 AC: 221 AN: 1364012 Hom.: 2 Cov.: 30 AF XY: 0.000214 AC XY: 144 AN XY: 674400

Gnomad4 AFR exome AF: 0.0000355

Gnomad4 AMR exome AF: 0.000151

Gnomad4 ASJ exome AF: 0.0000837

Gnomad4 EAS exome AF: 0.0000312

Gnomad4 SAS exome AF: 0.00244

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000559

Gnomad4 OTH exome AF: 0.000247

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152112 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74374

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000943 Hom.: 0

Bravo AF: 0.0000227

Asia WGS AF: 0.00116 AC: 4 AN: 3462

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Deficiency of malonyl-CoA decarboxylase Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 02, 2020

- -

MLYCD-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 20, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	12
Dann	Benign	0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs561775245; hg19: chr16-83933016;