rs1127368

Variant names:

• chr16-83915471-A-G
• rs1127368
• NM_012213.3:c.1464A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_012213.3(MLYCD):​c.1464A>G​(p.Gln488Gln) variant causes a synonymous change. The variant allele was found at a frequency of 0.00205 in 1,612,274 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0081 (13 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (26 hom.)
• Consequence: MLYCD NM_012213.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.81
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 16-83915471-A-G is Benign according to our data. Variant chr16-83915471-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 320740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00807 (1229/152350) while in subpopulation AFR AF = 0.0268 (1112/41570). AF 95% confidence interval is 0.0254. There are 13 homozygotes in GnomAd4. There are 587 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

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.1464A>G	p.Gln488Gln	synonymous	Exon 5 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.1464A>G	p.Gln488Gln	synonymous	Exon 5 of 5	ENSP00000262430.4
	MLYCD	ENST00000851351.1		c.1491A>G	p.Gln497Gln	synonymous	Exon 5 of 5	ENSP00000521410.1
	MLYCD	ENST00000851350.1		c.1314A>G	p.Gln438Gln	synonymous	Exon 4 of 4	ENSP00000521409.1

Frequencies

GnomAD3 genomes AF: 0.00806 AC: 1227 AN: 152232 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00379

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.00717

GnomAD2 exomes AF: 0.00241 AC: 588 AN: 243998 AF XY: 0.00191

Gnomad AFR exome AF: 0.0271

Gnomad AMR exome AF: 0.00264

Gnomad ASJ exome AF: 0.00121

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000628

Gnomad OTH exome AF: 0.00284

GnomAD4 exome AF: 0.00142 AC: 2078 AN: 1459924 Hom.: 26 Cov.: 30 AF XY: 0.00135 AC XY: 979 AN XY: 726302

African (AFR) AF: 0.0303 AC: 1013 AN: 33474

American (AMR) AF: 0.00273 AC: 122 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000765 AC: 20 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51536

Middle Eastern (MID) AF: 0.00539 AC: 31 AN: 5754

European-Non Finnish (NFE) AF: 0.000631 AC: 702 AN: 1111978

Other (OTH) AF: 0.00310 AC: 187 AN: 60374

GnomAD4 genome AF: 0.00807 AC: 1229 AN: 152350 Hom.: 13 Cov.: 33 AF XY: 0.00788 AC XY: 587 AN XY: 74506

African (AFR) AF: 0.0268 AC: 1112 AN: 41570

American (AMR) AF: 0.00379 AC: 58 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68034

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00351 Hom.: 4

Bravo AF: 0.00913

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000830

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.9
DANN	Benign	0.65
PhyloP100		3.8
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: rs1127368; hg19: chr16-83949076; COSMIC: COSV99299517;