1-220756014-T-C

Variant names:

• chr1-220756014-T-C
• rs1494373
• NM_017898.5:c.446+894T>C

Variant summary

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

The NM_017898.5(MTARC2):​c.446+894T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,226 control chromosomes in the GnomAD database, including 1,820 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 (1820 hom., cov: 33)
• Consequence: MTARC2 NM_017898.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• Publications: 17 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017898.5. 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
	MTARC2	NM_017898.5	MANE Select	c.446+894T>C		intron	N/A	NP_060368.2
	MTARC2	NM_001317338.2		c.446+894T>C		intron	N/A	NP_001304267.1	Q969Z3-1
	MTARC2	NM_001331042.2		c.446+894T>C		intron	N/A	NP_001317971.1	Q969Z3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTARC2	ENST00000366913.8	TSL:1 MANE Select	c.446+894T>C		intron	N/A	ENSP00000355880.3	Q969Z3-1
	MTARC2	ENST00000359316.6	TSL:1	c.446+894T>C		intron	N/A	ENSP00000352266.2	Q969Z3-2
	MTARC2	ENST00000866789.1		c.446+894T>C		intron	N/A	ENSP00000536848.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20273 AN: 152108 Hom.: 1812 Cov.: 33

Gnomad AFR AF: 0.0484

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.133 AC: 20287 AN: 152226 Hom.: 1820 Cov.: 33 AF XY: 0.138 AC XY: 10289 AN XY: 74446

African (AFR) AF: 0.0484 AC: 2011 AN: 41550

American (AMR) AF: 0.243 AC: 3710 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3470

East Asian (EAS) AF: 0.256 AC: 1322 AN: 5170

South Asian (SAS) AF: 0.200 AC: 963 AN: 4824

European-Finnish (FIN) AF: 0.175 AC: 1861 AN: 10608

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.139 AC: 9436 AN: 68002

Other (OTH) AF: 0.146 AC: 308 AN: 2112

Alfa AF: 0.142 Hom.: 3290

Bravo AF: 0.140

Asia WGS AF: 0.206 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.67
PhyloP100		-0.28
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: rs1494373; hg19: chr1-220929356;