rs555482480

Variant names:

• chr16-83899651-G-A
• rs555482480
• NM_012213.3:c.507G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-83899651-G-A
• chr16-83899651-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_012213.3(MLYCD):​c.507G>A​(p.Leu169Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000842 in 1,541,348 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L169L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00086 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00084 (0 hom.)
• Consequence: MLYCD NM_012213.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.366
• 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: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet, PanelApp Australia

ENSG00000288849 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 16-83899651-G-A is Benign according to our data. Variant chr16-83899651-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 378148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.366 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.507G>A	p.Leu169Leu	synonymous	Exon 1 of 5	NP_036345.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLYCD	ENST00000262430.6	TSL:1 MANE Select	c.507G>A	p.Leu169Leu	synonymous	Exon 1 of 5	ENSP00000262430.4
	MLYCD	ENST00000851351.1		c.507G>A	p.Leu169Leu	synonymous	Exon 1 of 5	ENSP00000521410.1
	MLYCD	ENST00000851350.1		c.507G>A	p.Leu169Leu	synonymous	Exon 1 of 4	ENSP00000521409.1

Frequencies

GnomAD3 genomes AF: 0.000860 AC: 131 AN: 152274 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00103 AC: 140 AN: 136154 AF XY: 0.00106

Gnomad AFR exome AF: 0.000182

Gnomad AMR exome AF: 0.000964

Gnomad ASJ exome AF: 0.00707

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000962

Gnomad OTH exome AF: 0.00173

GnomAD4 exome AF: 0.000840 AC: 1167 AN: 1388956 Hom.: 0 Cov.: 30 AF XY: 0.000820 AC XY: 563 AN XY: 686676

African (AFR) AF: 0.000195 AC: 6 AN: 30802

American (AMR) AF: 0.00139 AC: 51 AN: 36662

Ashkenazi Jewish (ASJ) AF: 0.00676 AC: 169 AN: 24982

East Asian (EAS) AF: 0.00 AC: 0 AN: 35460

South Asian (SAS) AF: 0.0000249 AC: 2 AN: 80170

European-Finnish (FIN) AF: 0.0000877 AC: 3 AN: 34198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4886

European-Non Finnish (NFE) AF: 0.000796 AC: 863 AN: 1083756

Other (OTH) AF: 0.00126 AC: 73 AN: 58040

GnomAD4 genome AF: 0.000860 AC: 131 AN: 152392 Hom.: 1 Cov.: 33 AF XY: 0.000778 AC XY: 58 AN XY: 74530

African (AFR) AF: 0.000168 AC: 7 AN: 41602

American (AMR) AF: 0.00209 AC: 32 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000926 AC: 63 AN: 68032

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00175 Hom.: 0

Bravo AF: 0.00112

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Deficiency of malonyl-CoA decarboxylase (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Benign	0.96
PhyloP100		0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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

dbSNP: rs555482480; hg19: chr16-83933256;