rs201576638

Variant names:

• chr16-83915182-G-A
• rs201576638
• NM_012213.3:c.1175G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-83915182-G-A
• chr16-83915182-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_012213.3(MLYCD):​c.1175G>A​(p.Arg392Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R392W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: MLYCD NM_012213.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.299
• Publications: 3 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.054446697).

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.1175G>A	p.Arg392Gln	missense	Exon 5 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.1175G>A	p.Arg392Gln	missense	Exon 5 of 5	ENSP00000262430.4	O95822-1
	MLYCD	ENST00000851351.1		c.1202G>A	p.Arg401Gln	missense	Exon 5 of 5	ENSP00000521410.1
	MLYCD	ENST00000851350.1		c.1025G>A	p.Arg342Gln	missense	Exon 4 of 4	ENSP00000521409.1

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000802 AC: 20 AN: 249240 AF XY: 0.0000887

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000166 AC: 242 AN: 1461730 Hom.: 0 Cov.: 30 AF XY: 0.000157 AC XY: 114 AN XY: 727150

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.000202 AC: 225 AN: 1111896

Other (OTH) AF: 0.000149 AC: 9 AN: 60378

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15 AN XY: 74368

African (AFR) AF: 0.0000241 AC: 1 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68044

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000228 Hom.: 0

Bravo AF: 0.000121

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000355 AC: 3

ExAC AF: 0.0000909 AC: 11

EpiCase AF: 0.000273

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.1
DANN	Benign	0.95
DEOGEN2	Benign	0.086	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.30
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.095
Sift	Benign	0.54	T
Sift4G	Benign	0.55	T
Polyphen		0.011	B
Vest4		0.036
MVP		0.89
MPC		0.019
ClinPred		0.019	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.093
gMVP		0.30
Mutation Taster		=91/9	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: rs201576638; hg19: chr16-83948787;