rs12407624

Variant names:

• chr1-220753502-G-A
• rs12407624
• NM_017898.5:c.273-1445G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017898.5(MTARC2):​c.273-1445G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,158 control chromosomes in the GnomAD database, including 1,762 homozygotes. 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: 𝑓 0.13 (1762 hom., cov: 32)
• Consequence: MTARC2 NM_017898.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 2 publications found

Genes affected

MTARC2 (HGNC:26064): (mitochondrial amidoxime reducing component 2) The protein encoded by this gene is an enzyme found in the outer mitochondrial membrane that reduces N-hydroxylated substrates. The encoded protein uses molybdenum as a cofactor and cytochrome b5 type B and NADH cytochrome b5 reductase as accessory proteins. One type of substrate used is N-hydroxylated nucleotide base analogues, which can be toxic to a cell. Other substrates include N(omega)-hydroxy-L-arginine (NOHA) and amidoxime prodrugs, which are activated by the encoded enzyme. Multiple transcript variants encoding the different isoforms have been found for this gene. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTARC2	NM_017898.5	c.273-1445G>A		intron_variant	Intron 1 of 7	ENST00000366913.8	NP_060368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTARC2	ENST00000366913.8	c.273-1445G>A		intron_variant	Intron 1 of 7	1	NM_017898.5	ENSP00000355880.3
MTARC2	ENST00000359316.6	c.273-1445G>A		intron_variant	Intron 1 of 4	1		ENSP00000352266.2
MTARC2	ENST00000469583.1	n.273-866G>A		intron_variant	Intron 1 of 2	3		ENSP00000435450.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19974 AN: 152040 Hom.: 1754 Cov.: 32

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.144

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.131 AC: 19992 AN: 152158 Hom.: 1762 Cov.: 32 AF XY: 0.136 AC XY: 10134 AN XY: 74394

African (AFR) AF: 0.0483 AC: 2006 AN: 41528

American (AMR) AF: 0.238 AC: 3635 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3472

East Asian (EAS) AF: 0.248 AC: 1278 AN: 5146

South Asian (SAS) AF: 0.186 AC: 896 AN: 4820

European-Finnish (FIN) AF: 0.175 AC: 1858 AN: 10608

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9340 AN: 67982

Other (OTH) AF: 0.142 AC: 299 AN: 2112

Alfa AF: 0.143 Hom.: 919

Bravo AF: 0.139

Asia WGS AF: 0.198 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.75
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs12407624; hg19: chr1-220926844;