rs2278037

Positions:

chr16-83908121-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012213.3(MLYCD):c.642-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 1,613,708 control chromosomes in the GnomAD database, including 3,127 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 477 hom., cov: 33)

Exomes 𝑓: 0.054 ( 2650 hom. )

Consequence

MLYCD
NM_012213.3 splice_region, intron

Scores

Splicing: ADA: 0.00001181

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.97

Variant links:

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]

MLYCD links:

ENSG00000288849 (HGNC:):

ENSG00000288849 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 16-83908121-C-T is Benign according to our data. Variant chr16-83908121-C-T is described in ClinVar as [Benign]. Clinvar id is 95503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-83908121-C-T is described in Lovd as [Benign]. Variant chr16-83908121-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLYCD	NM_012213.3 linkuse as main transcript	c.642-5C>T		splice_region_variant, intron_variant		ENST00000262430.6	NP_036345.2	O95822-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MLYCD	ENST00000262430.6 linkuse as main transcript	c.642-5C>T	splice_region_variant, intron_variant	1	NM_012213.3	ENSP00000262430.4	O95822-1
ENSG00000288849	ENST00000689373.1 linkuse as main transcript	n.1315-5C>T	splice_region_variant, intron_variant
ENSG00000288849	ENST00000692462.1 linkuse as main transcript	n.1283-5C>T	splice_region_variant, intron_variant
MLYCD	ENST00000561562.5 linkuse as main transcript	c.-12C>T	upstream_gene_variant	2		ENSP00000484042.1	A0A087X1B8

Frequencies

GnomAD3 genomes

AF:

0.0725

AC:

11031

AN:

152122

Hom.:

471

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.0221

Gnomad FIN

AF:

0.0660

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0514

Gnomad OTH

AF:

0.0526

GnomAD3 exomes

AF:

0.0643

AC:

16027

AN:

249438

Hom.:

699

AF XY:

0.0583

AC XY:

7896

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.121

Gnomad SAS exome

AF:

0.0174

Gnomad FIN exome

AF:

0.0634

Gnomad NFE exome

AF:

0.0491

Gnomad OTH exome

AF:

0.0591

GnomAD4 exome

AF:

0.0538

AC:

78647

AN:

1461468

Hom.:

2650

Cov.:

AF XY:

0.0519

AC XY:

37716

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.108

Gnomad4 AMR exome

AF:

0.126

Gnomad4 ASJ exome

AF:

0.00494

Gnomad4 EAS exome

AF:

0.141

Gnomad4 SAS exome

AF:

0.0181

Gnomad4 FIN exome

AF:

0.0649

Gnomad4 NFE exome

AF:

0.0499

Gnomad4 OTH exome

AF:

0.0508

GnomAD4 genome

AF:

0.0727

AC:

11062

AN:

152240

Hom.:

477

Cov.:

AF XY:

0.0737

AC XY:

5483

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.103

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.112

Gnomad4 SAS

AF:

0.0215

Gnomad4 FIN

AF:

0.0660

Gnomad4 NFE

AF:

0.0515

Gnomad4 OTH

AF:

0.0525

Alfa

AF:

0.0509

Hom.:

517

Bravo

AF:

0.0780

Asia WGS

AF:

0.0790

AC:

273

AN:

3478

EpiCase

AF:

0.0419

EpiControl

AF:

0.0436

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deficiency of malonyl-CoA decarboxylase

Benign:5

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 07, 2013	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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 28, 2012	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.0070

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over