1-220767069-T-C

Variant names:

• chr1-220767069-T-C
• rs337147
• NM_017898.5:c.750+4019T>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.750+4019T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,840 control chromosomes in the GnomAD database, including 12,189 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 0.36 (12189 hom., cov: 31)
• Consequence: MTARC2 NM_017898.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.934
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTARC2	NM_017898.5	c.750+4019T>C		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.750+4019T>C		intron_variant	Intron 4 of 7	1	NM_017898.5	ENSP00000355880.3
MTARC2	ENST00000359316.6	c.750+4019T>C		intron_variant	Intron 4 of 4	1		ENSP00000352266.2
MTARC2	ENST00000425560.1	c.453+4019T>C		intron_variant	Intron 3 of 3	3		ENSP00000416442.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54123 AN: 151722 Hom.: 12154 Cov.: 31

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.357 AC: 54211 AN: 151840 Hom.: 12189 Cov.: 31 AF XY: 0.363 AC XY: 26955 AN XY: 74198

African (AFR) AF: 0.576 AC: 23801 AN: 41356

American (AMR) AF: 0.418 AC: 6380 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 967 AN: 3470

East Asian (EAS) AF: 0.749 AC: 3865 AN: 5158

South Asian (SAS) AF: 0.388 AC: 1863 AN: 4800

European-Finnish (FIN) AF: 0.235 AC: 2475 AN: 10528

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13874 AN: 67970

Other (OTH) AF: 0.342 AC: 720 AN: 2104

Alfa AF: 0.269 Hom.: 18547

Bravo AF: 0.386

Asia WGS AF: 0.568 AC: 1971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.65
PhyloP100		-0.93
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: rs337147; hg19: chr1-220940411;