rs3815806

Variant names:

• chr16-83906979-C-T
• rs3815806
• NM_012213.3:c.529-8C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-83906979-C-T
• chr16-83906979-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012213.3(MLYCD):​c.529-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 1,612,944 control chromosomes in the GnomAD database, including 1,753 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (760 hom., cov: 33)
  • Exomes 𝑓: 0.019 (993 hom.)
• Consequence: MLYCD NM_012213.3 splice_region, intron
• Scores: Splicing: ADA: 0.00004206
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.643
• Publications: 7 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=-0.82).
• BP6: Variant 16-83906979-C-T is Benign according to our data. Variant chr16-83906979-C-T is described in ClinVar as Benign. ClinVar VariationId is 320726.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

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.529-8C>T		splice_region 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.529-8C>T		splice_region intron	N/A	ENSP00000262430.4	O95822-1
	MLYCD	ENST00000851351.1		c.548C>T	p.Pro183Leu	missense	Exon 2 of 5	ENSP00000521410.1
	MLYCD	ENST00000851350.1		c.529-8C>T		splice_region intron	N/A	ENSP00000521409.1

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9831 AN: 152046 Hom.: 756 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0333

Gnomad ASJ AF: 0.0257

Gnomad EAS AF: 0.0889

Gnomad SAS AF: 0.0390

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0465

GnomAD2 exomes AF: 0.0329 AC: 8214 AN: 249570 AF XY: 0.0308

Gnomad AFR exome AF: 0.189

Gnomad AMR exome AF: 0.0170

Gnomad ASJ exome AF: 0.0208

Gnomad EAS exome AF: 0.0847

Gnomad FIN exome AF: 0.0141

Gnomad NFE exome AF: 0.0124

Gnomad OTH exome AF: 0.0259

GnomAD4 exome AF: 0.0186 AC: 27202 AN: 1460780 Hom.: 993 Cov.: 31 AF XY: 0.0186 AC XY: 13554 AN XY: 726776

African (AFR) AF: 0.192 AC: 6411 AN: 33428

American (AMR) AF: 0.0193 AC: 861 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0215 AC: 562 AN: 26120

East Asian (EAS) AF: 0.0736 AC: 2920 AN: 39684

South Asian (SAS) AF: 0.0355 AC: 3060 AN: 86242

European-Finnish (FIN) AF: 0.0130 AC: 692 AN: 53410

Middle Eastern (MID) AF: 0.0274 AC: 158 AN: 5764

European-Non Finnish (NFE) AF: 0.00950 AC: 10550 AN: 1111046

Other (OTH) AF: 0.0329 AC: 1988 AN: 60364

GnomAD4 genome AF: 0.0647 AC: 9849 AN: 152164 Hom.: 760 Cov.: 33 AF XY: 0.0635 AC XY: 4722 AN XY: 74404

African (AFR) AF: 0.185 AC: 7671 AN: 41486

American (AMR) AF: 0.0333 AC: 509 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0257 AC: 89 AN: 3468

East Asian (EAS) AF: 0.0885 AC: 457 AN: 5162

South Asian (SAS) AF: 0.0392 AC: 189 AN: 4818

European-Finnish (FIN) AF: 0.0101 AC: 107 AN: 10610

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0106 AC: 720 AN: 68016

Other (OTH) AF: 0.0465 AC: 98 AN: 2108

Alfa AF: 0.0364 Hom.: 751

Bravo AF: 0.0720

Asia WGS AF: 0.0830 AC: 291 AN: 3478

EpiCase AF: 0.0119

EpiControl AF: 0.0116

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.64
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000042
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.010		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: rs3815806; hg19: chr16-83940584; COSMIC: COSV107277159; COSMIC: COSV107277159;