Genetic Variant MLYCD:p.Thr9Thr (chr16-83899171-G-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_012213.3(MLYCD):c.27G>T(p.Thr9Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. T9T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MLYCD
NM_012213.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.699

Publications

0 publications found

Variant links:

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, Orphanet, PanelApp Australia, G2P

MLYCD links:

ENSG00000288849 (HGNC:):

ENSG00000288849 links:

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ACMG classification

Classification was made for transcript

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=-0.75).

BP6

Variant 16-83899171-G-T is Benign according to our data. Variant chr16-83899171-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2768870.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.699 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.27G>T	p.Thr9Thr	synonymous	Exon 1 of 5	NP_036345.2	O95822-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MLYCD	ENST00000262430.6	TSL:1 MANE Select	c.27G>T	p.Thr9Thr	synonymous	Exon 1 of 5	ENSP00000262430.4	O95822-1
MLYCD	ENST00000851351.1		c.27G>T	p.Thr9Thr	synonymous	Exon 1 of 5	ENSP00000521410.1
MLYCD	ENST00000851350.1		c.27G>T	p.Thr9Thr	synonymous	Exon 1 of 4	ENSP00000521409.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1015192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

487484

African (AFR)

AF:

0.00

AC:

AN:

19850

American (AMR)

AF:

0.00

AC:

AN:

6580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10800

East Asian (EAS)

AF:

0.00

AC:

AN:

15402

South Asian (SAS)

AF:

0.00

AC:

AN:

24686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2504

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

881308

Other (OTH)

AF:

0.00

AC:

AN:

37790

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Deficiency of malonyl-CoA decarboxylase (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.7

(source)

DANN

Benign

0.77

PhyloP100

-0.70

PromoterAI

0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over