NM_012213.3:c.24G>A

Variant names:

• chr16-83899168-G-A
• NM_012213.3:c.24G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_012213.3(MLYCD):​c.24G>A​(p.Leu8Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,013,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: MLYCD NM_012213.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0970
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 16-83899168-G-A is Benign according to our data. Variant chr16-83899168-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2775993.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.097 with no splicing effect.

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.24G>A	p.Leu8Leu	synonymous	Exon 1 of 5	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.24G>A	p.Leu8Leu	synonymous	Exon 1 of 5	ENSP00000262430.4	O95822-1
	MLYCD	ENST00000851351.1		c.24G>A	p.Leu8Leu	synonymous	Exon 1 of 5	ENSP00000521410.1
	MLYCD	ENST00000851350.1		c.24G>A	p.Leu8Leu	synonymous	Exon 1 of 4	ENSP00000521409.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000148 AC: 15 AN: 1013558 Hom.: 0 Cov.: 28 AF XY: 0.0000164 AC XY: 8 AN XY: 486544

African (AFR) AF: 0.00 AC: 0 AN: 19816

American (AMR) AF: 0.00 AC: 0 AN: 6590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10726

East Asian (EAS) AF: 0.00 AC: 0 AN: 15304

South Asian (SAS) AF: 0.00 AC: 0 AN: 24560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2496

European-Non Finnish (NFE) AF: 0.0000170 AC: 15 AN: 880218

Other (OTH) AF: 0.00 AC: 0 AN: 37720

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Deficiency of malonyl-CoA decarboxylase (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.4
DANN	Benign	0.96
PhyloP100		0.097
PromoterAI		0.042	Neutral

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

hg19: chr16-83932773;