16-83899122-C-A

Variant names:

• chr16-83899122-C-A
• rs867271136
• NM_012213.3:c.-23C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_012213.3(MLYCD):​c.-23C>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 0.0000371 in 1,106,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: MLYCD NM_012213.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.50
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-83899122-C-A is Benign according to our data. Variant chr16-83899122-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 510978.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-23C>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.-23C>A		5_prime_UTR	Exon 1 of 5	ENSP00000262430.4	O95822-1
	ENSG00000288849	ENST00000689373.1		n.1202-7865C>A		intron	N/A
	ENSG00000288849	ENST00000692462.1		n.1170-7865C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 149942 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000408 AC: 39 AN: 956566 Hom.: 0 Cov.: 28 AF XY: 0.0000310 AC XY: 14 AN XY: 452136

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000537 AC: 1 AN: 18610

American (AMR) AF: 0.00 AC: 0 AN: 4782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8918

East Asian (EAS) AF: 0.000165 AC: 2 AN: 12088

South Asian (SAS) AF: 0.00 AC: 0 AN: 19470

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2272

European-Non Finnish (NFE) AF: 0.0000427 AC: 36 AN: 843110

Other (OTH) AF: 0.00 AC: 0 AN: 34594

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000117597), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 149942 Hom.: 0 Cov.: 33 AF XY: 0.0000137 AC XY: 1 AN XY: 73128

African (AFR) AF: 0.0000243 AC: 1 AN: 41210

American (AMR) AF: 0.00 AC: 0 AN: 15092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67120

Other (OTH) AF: 0.00 AC: 0 AN: 2058

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.4
DANN	Benign	0.65
PhyloP100		-1.5
PromoterAI		0.041	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs867271136; hg19: chr16-83932727;