16-83899138-G-A

Variant names:

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

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.-7G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,130,800 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (6 hom., cov: 33)
  • Exomes 𝑓: 0.00046 (5 hom.)
• Consequence: MLYCD NM_012213.3 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 16-83899138-G-A is Benign according to our data. Variant chr16-83899138-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 383059.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 = 0.00574 (860/149850) while in subpopulation AFR AF = 0.0199 (820/41284). AF 95% confidence interval is 0.0187. There are 6 homozygotes in GnomAd4. There are 407 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 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.-7G>A		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>A		5_prime_UTR	Exon 1 of 5	ENSP00000262430.4	O95822-1
	MLYCD	ENST00000851351.1		c.-7G>A		5_prime_UTR	Exon 1 of 5	ENSP00000521410.1
	MLYCD	ENST00000851350.1		c.-7G>A		5_prime_UTR	Exon 1 of 4	ENSP00000521409.1

Frequencies

GnomAD3 genomes AF: 0.00565 AC: 846 AN: 149742 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00186

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000895

Gnomad OTH AF: 0.00243

GnomAD2 exomes AF: 0.000307 AC: 2 AN: 6508 AF XY: 0.000237

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: 0.000371

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000459 AC: 450 AN: 980950 Hom.: 5 Cov.: 28 AF XY: 0.000435 AC XY: 203 AN XY: 467106

African (AFR) AF: 0.0199 AC: 380 AN: 19094

American (AMR) AF: 0.00146 AC: 8 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: 0.0000461 AC: 1 AN: 21688

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

Middle Eastern (MID) AF: 0.000837 AC: 2 AN: 2390

European-Non Finnish (NFE) AF: 0.0000233 AC: 20 AN: 859320

Other (OTH) AF: 0.00109 AC: 39 AN: 35844

GnomAD4 genome AF: 0.00574 AC: 860 AN: 149850 Hom.: 6 Cov.: 33 AF XY: 0.00556 AC XY: 407 AN XY: 73160

African (AFR) AF: 0.0199 AC: 820 AN: 41284

American (AMR) AF: 0.00186 AC: 28 AN: 15086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9768

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0000895 AC: 6 AN: 67036

Other (OTH) AF: 0.00240 AC: 5 AN: 2082

Alfa AF: 0.00200 Hom.: 0

Asia WGS AF: 0.00324 AC: 10 AN: 3102

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.29
DANN	Benign	0.92
PhyloP100		-3.6
PromoterAI		0.049	Neutral
Mutation Taster		=300/0	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: rs9930103; hg19: chr16-83932743;