1-220767069-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• 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/exons	MANE	UniProt
MTARC2	NM_017898.5	c.750+4019T>C		intron_variant		ENST00000366913.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTARC2	ENST00000366913.8	c.750+4019T>C		intron_variant		1	NM_017898.5	P1
MTARC2	ENST00000359316.6	c.750+4019T>C		intron_variant		1
MTARC2	ENST00000425560.1	c.453+4019T>C		intron_variant		3

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

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.342

Alfa AF: 0.243 Hom.: 8921

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

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: rs337147; hg19: chr1-220940411;