rs2278037

Variant names:

• chr16-83908121-C-T
• rs2278037
• NM_012213.3:c.642-5C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Publications: 10 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]

MLYCD Gene-Disease associations (from GenCC):

• malonic aciduria

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet

ENSG00000288849 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 95503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012213.3. 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
	MLYCD	NM_012213.3	MANE Select	c.642-5C>T		splice_region intron	N/A	NP_036345.2	O95822-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLYCD	ENST00000262430.6	TSL:1 MANE Select	c.642-5C>T		splice_region intron	N/A	ENSP00000262430.4	O95822-1
	MLYCD	ENST00000851351.1		c.669-5C>T		splice_region intron	N/A	ENSP00000521410.1
	MLYCD	ENST00000851350.1		c.642-5C>T		splice_region intron	N/A	ENSP00000521409.1

Frequencies

GnomAD3 genomes AF: 0.0725 AC: 11031 AN: 152122 Hom.: 471 Cov.: 33

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

GnomAD2 exomes AF: 0.0643 AC: 16027 AN: 249438 AF XY: 0.0583

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 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.: 32 AF XY: 0.0519 AC XY: 37716 AN XY: 727030

African (AFR) AF: 0.108 AC: 3617 AN: 33470

American (AMR) AF: 0.126 AC: 5639 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00494 AC: 129 AN: 26136

East Asian (EAS) AF: 0.141 AC: 5584 AN: 39692

South Asian (SAS) AF: 0.0181 AC: 1565 AN: 86254

European-Finnish (FIN) AF: 0.0649 AC: 3468 AN: 53406

Middle Eastern (MID) AF: 0.0149 AC: 86 AN: 5768

European-Non Finnish (NFE) AF: 0.0499 AC: 55492 AN: 1111656

Other (OTH) AF: 0.0508 AC: 3067 AN: 60390

GnomAD4 genome AF: 0.0727 AC: 11062 AN: 152240 Hom.: 477 Cov.: 33 AF XY: 0.0737 AC XY: 5483 AN XY: 74440

African (AFR) AF: 0.106 AC: 4414 AN: 41528

American (AMR) AF: 0.103 AC: 1572 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3470

East Asian (EAS) AF: 0.112 AC: 582 AN: 5174

South Asian (SAS) AF: 0.0215 AC: 104 AN: 4830

European-Finnish (FIN) AF: 0.0660 AC: 700 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0515 AC: 3500 AN: 68020

Other (OTH) AF: 0.0525 AC: 111 AN: 2114

Alfa AF: 0.0559 Hom.: 1183

Bravo AF: 0.0780

Asia WGS AF: 0.0790 AC: 273 AN: 3478

EpiCase AF: 0.0419

EpiControl AF: 0.0436

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Deficiency of malonyl-CoA decarboxylase (5)
-	-	3	not specified (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0070
DANN	Benign	0.58
PhyloP100		-2.0
PromoterAI		-0.0070	Neutral
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2278037; hg19: chr16-83941726; COSMIC: COSV52306069; COSMIC: COSV52306069;