rs62640903

Variant names:

• chr16-83912269-A-G
• rs62640903
• NM_012213.3:c.850A>G

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.850A>G​(p.Thr284Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,614,196 control chromosomes in the GnomAD database, including 368 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (191 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (177 hom.)
• Consequence: MLYCD NM_012213.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.469
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028628707).
• BP6: Variant 16-83912269-A-G is Benign according to our data. Variant chr16-83912269-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 138232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0899 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.850A>G	p.Thr284Ala	missense	Exon 4 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.850A>G	p.Thr284Ala	missense	Exon 4 of 5	ENSP00000262430.4	O95822-1
	MLYCD	ENST00000851351.1		c.877A>G	p.Thr293Ala	missense	Exon 4 of 5	ENSP00000521410.1
	MLYCD	ENST00000561562.5	TSL:2	c.202A>G	p.Thr68Ala	missense	Exon 2 of 4	ENSP00000484042.1	A0A087X1B8

Frequencies

GnomAD3 genomes AF: 0.0263 AC: 3997 AN: 152186 Hom.: 185 Cov.: 32

Gnomad AFR AF: 0.0919

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00700

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00463

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00670 AC: 1671 AN: 249576 AF XY: 0.00503

Gnomad AFR exome AF: 0.0938

Gnomad AMR exome AF: 0.00321

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00406

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.00279 AC: 4073 AN: 1461892 Hom.: 177 Cov.: 31 AF XY: 0.00241 AC XY: 1756 AN XY: 727248

African (AFR) AF: 0.0951 AC: 3184 AN: 33478

American (AMR) AF: 0.00371 AC: 166 AN: 44724

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

East Asian (EAS) AF: 0.00184 AC: 73 AN: 39700

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.000214 AC: 238 AN: 1112012

Other (OTH) AF: 0.00598 AC: 361 AN: 60396

GnomAD4 genome AF: 0.0264 AC: 4025 AN: 152304 Hom.: 191 Cov.: 32 AF XY: 0.0254 AC XY: 1891 AN XY: 74472

African (AFR) AF: 0.0923 AC: 3836 AN: 41544

American (AMR) AF: 0.00699 AC: 107 AN: 15302

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

East Asian (EAS) AF: 0.00483 AC: 25 AN: 5172

South Asian (SAS) AF: 0.000827 AC: 4 AN: 4834

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68038

Other (OTH) AF: 0.0166 AC: 35 AN: 2112

Alfa AF: 0.00992 Hom.: 114

Bravo AF: 0.0298

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0937 AC: 370

ESP6500EA AF: 0.000241 AC: 2

ExAC AF: 0.00834 AC: 1008

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

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
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	3.0
DANN	Benign	0.42
DEOGEN2	Benign	0.29	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.021	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.91	L
PhyloP100		0.47
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.27
Sift	Benign	0.53	T
Sift4G	Benign	0.64	T
Polyphen		0.0010	B
Vest4		0.12
MVP		0.90
MPC		0.019
ClinPred		0.0013	T
GERP RS		0.52
Varity_R		0.13
gMVP		0.33
Mutation Taster		=100/0	polymorphism (auto)

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: rs62640903; hg19: chr16-83945874;