16-83912202-C-T

Position:

• chr16-83912202-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_012213.3(MLYCD):​c.799-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00455 in 1,614,162 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0046 (19 hom.)
• Consequence: MLYCD NM_012213.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.775

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-83912202-C-T is Benign according to our data. Variant chr16-83912202-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 381435.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-83912202-C-T is described in Lovd as [Benign]. Variant chr16-83912202-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00391 (595/152330) while in subpopulation NFE AF= 0.0056 (381/68036). AF 95% confidence interval is 0.00514. There are 4 homozygotes in gnomad4. There are 321 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLYCD	NM_012213.3	c.799-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000262430.6	NP_036345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLYCD	ENST00000262430.6	c.799-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_012213.3	ENSP00000262430	P1

Frequencies

GnomAD3 genomes AF: 0.00390 AC: 594 AN: 152212 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00405

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00904

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00560

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00306 AC: 764 AN: 249570 Hom.: 2 AF XY: 0.00313 AC XY: 424 AN XY: 135400

Gnomad AFR exome AF: 0.000839

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00208

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00691

Gnomad NFE exome AF: 0.00454

Gnomad OTH exome AF: 0.00297

GnomAD4 exome AF: 0.00462 AC: 6755 AN: 1461832 Hom.: 19 Cov.: 31 AF XY: 0.00450 AC XY: 3274 AN XY: 727214

Gnomad4 AFR exome AF: 0.000866

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.00253

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00702

Gnomad4 NFE exome AF: 0.00539

Gnomad4 OTH exome AF: 0.00382

GnomAD4 genome AF: 0.00391 AC: 595 AN: 152330 Hom.: 4 Cov.: 33 AF XY: 0.00431 AC XY: 321 AN XY: 74478

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00405

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00904

Gnomad4 NFE AF: 0.00560

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00362 Hom.: 0

Bravo AF: 0.00306

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Deficiency of malonyl-CoA decarboxylase Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 01, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jun 02, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.32

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: rs150789545; hg19: chr16-83945807;