rs17008643

Variant names:

• chr1-220774441-A-G
• rs17008643
• NM_017898.5:c.751-5577A>G

Variant summary

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

The NM_017898.5(MTARC2):​c.751-5577A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0472 in 152,250 control chromosomes in the GnomAD database, including 266 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 0.047 (266 hom., cov: 32)
• Consequence: MTARC2 NM_017898.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTARC2	NM_017898.5	c.751-5577A>G		intron_variant	Intron 4 of 7	ENST00000366913.8	NP_060368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTARC2	ENST00000366913.8	c.751-5577A>G		intron_variant	Intron 4 of 7	1	NM_017898.5	ENSP00000355880.3
MTARC2	ENST00000359316.6	c.751-9478A>G		intron_variant	Intron 4 of 4	1		ENSP00000352266.2
MTARC2	ENST00000425560.1	c.454-5577A>G		intron_variant	Intron 3 of 3	3		ENSP00000416442.1

Frequencies

GnomAD3 genomes AF: 0.0472 AC: 7178 AN: 152134 Hom.: 265 Cov.: 32

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.0656

Gnomad FIN AF: 0.0489

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0468

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

GnomAD4 genome AF: 0.0472 AC: 7186 AN: 152250 Hom.: 266 Cov.: 32 AF XY: 0.0483 AC XY: 3594 AN XY: 74432

African (AFR) AF: 0.0473 AC: 1963 AN: 41542

American (AMR) AF: 0.0311 AC: 476 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0680 AC: 236 AN: 3472

East Asian (EAS) AF: 0.192 AC: 994 AN: 5182

South Asian (SAS) AF: 0.0647 AC: 312 AN: 4824

European-Finnish (FIN) AF: 0.0489 AC: 518 AN: 10600

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0364 AC: 2477 AN: 68020

Other (OTH) AF: 0.0487 AC: 103 AN: 2116

Alfa AF: 0.0399 Hom.: 70

Bravo AF: 0.0445

Asia WGS AF: 0.133 AC: 459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.60
DANN	Benign	0.32
PhyloP100		-0.35
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: rs17008643; hg19: chr1-220947783;