rs150789545

Variant names:

• chr16-83912202-C-T
• rs150789545
• NM_012213.3:c.799-16C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-83912202-C-T
• chr16-83912202-C-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.799-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00455 in 1,614,162 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0046 (19 hom.)
• Consequence: MLYCD NM_012213.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.775
• 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, G2P, Orphanet

ENSG00000288849 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-83912202-C-T is Benign according to our data. Variant chr16-83912202-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 381435.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00391 (595/152330) while in subpopulation NFE AF = 0.0056 (381/68036). AF 95% confidence interval is 0.00514. There are 4 homozygotes in GnomAd4. There are 321 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 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.799-16C>T		intron	N/A	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.799-16C>T		intron	N/A	ENSP00000262430.4	O95822-1
	MLYCD	ENST00000851351.1		c.826-16C>T		intron	N/A	ENSP00000521410.1
	MLYCD	ENST00000851350.1		c.799-2754C>T		intron	N/A	ENSP00000521409.1

Frequencies

GnomAD3 genomes AF: 0.00390 AC: 594 AN: 152212 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00405

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00904

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00560

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00306 AC: 764 AN: 249570 AF XY: 0.00313

Gnomad AFR exome AF: 0.000839

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00208

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00691

Gnomad NFE exome AF: 0.00454

Gnomad OTH exome AF: 0.00297

GnomAD4 exome AF: 0.00462 AC: 6755 AN: 1461832 Hom.: 19 Cov.: 31 AF XY: 0.00450 AC XY: 3274 AN XY: 727214

African (AFR) AF: 0.000866 AC: 29 AN: 33478

American (AMR) AF: 0.00123 AC: 55 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00253 AC: 66 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00702 AC: 375 AN: 53412

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00539 AC: 5996 AN: 1111978

Other (OTH) AF: 0.00382 AC: 231 AN: 60396

GnomAD4 genome AF: 0.00391 AC: 595 AN: 152330 Hom.: 4 Cov.: 33 AF XY: 0.00431 AC XY: 321 AN XY: 74478

African (AFR) AF: 0.00101 AC: 42 AN: 41566

American (AMR) AF: 0.00405 AC: 62 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00904 AC: 96 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00560 AC: 381 AN: 68036

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00362 Hom.: 0

Bravo AF: 0.00306

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Deficiency of malonyl-CoA decarboxylase (2)
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.32
PhyloP100		-0.78
Mutation Taster		=100/0	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: rs150789545; hg19: chr16-83945807;