chr16-83899138-G-T

Variant names:

• chr16-83899138-G-T
• rs9930103
• NM_012213.3:c.-7G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012213.3(MLYCD):​c.-7G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000714 in 980,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: MLYCD NM_012213.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.56
• 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, PanelApp Australia, G2P

ENSG00000288849 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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.-7G>T		5_prime_UTR	Exon 1 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.-7G>T		5_prime_UTR	Exon 1 of 5	ENSP00000262430.4	O95822-1
	MLYCD	ENST00000851351.1		c.-7G>T		5_prime_UTR	Exon 1 of 5	ENSP00000521410.1
	MLYCD	ENST00000851350.1		c.-7G>T		5_prime_UTR	Exon 1 of 4	ENSP00000521409.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000714 AC: 7 AN: 980952 Hom.: 0 Cov.: 28 AF XY: 0.00000642 AC XY: 3 AN XY: 467106

African (AFR) AF: 0.00 AC: 0 AN: 19096

American (AMR) AF: 0.00 AC: 0 AN: 5492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9624

East Asian (EAS) AF: 0.00 AC: 0 AN: 13310

South Asian (SAS) AF: 0.00 AC: 0 AN: 21688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2390

European-Non Finnish (NFE) AF: 0.00000815 AC: 7 AN: 859320

Other (OTH) AF: 0.00 AC: 0 AN: 35844

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.23
DANN	Benign	0.43
PhyloP100		-3.6
PromoterAI		0.10	Neutral

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: rs9930103; hg19: chr16-83932743;