rs12407624

chr1-220753502-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MTARC2	NM_017898.5	c.273-1445G>A		intron_variant		ENST00000366913.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTARC2	ENST00000366913.8	c.273-1445G>A		intron_variant		1	NM_017898.5	P1
MTARC2	ENST00000359316.6	c.273-1445G>A		intron_variant		1
MTARC2	ENST00000469583.1	c.273-866G>A		intron_variant, NMD_transcript_variant		3

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

Gnomad4 AFR AF: 0.0483

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.142

Alfa AF: 0.143 Hom.: 824

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12407624; hg19: chr1-220926844;