rs6693017

Variant names:

• chr1-220803991-T-G
• rs6693017
• NM_022746.4:c.754-1061T>G

Variant summary

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

The NM_022746.4(MTARC1):​c.754-1061T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,152 control chromosomes in the GnomAD database, including 4,088 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 0.22 (4088 hom., cov: 32)
• Consequence: MTARC1 NM_022746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 9 publications found

Genes affected

MTARC1 (HGNC:26189): (mitochondrial amidoxime reducing component 1) Enables molybdenum ion binding activity; molybdopterin cofactor binding activity; and oxidoreductase activity, acting on other nitrogenous compounds as donors. Contributes to nitrite reductase (NO-forming) activity. Involved in cellular detoxification of nitrogen compound; nitrate metabolic process; and nitric oxide biosynthetic process. Located in mitochondrion. Part of nitric-oxide synthase complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286231 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTARC1	NM_022746.4	c.754-1061T>G		intron_variant	Intron 4 of 6	ENST00000366910.10	NP_073583.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTARC1	ENST00000366910.10	c.754-1061T>G		intron_variant	Intron 4 of 6	1	NM_022746.4	ENSP00000355877.5
ENSG00000286231	ENST00000651706.1	n.709-1061T>G		intron_variant	Intron 4 of 8			ENSP00000499157.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32866 AN: 152034 Hom.: 4068 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.216 AC: 32917 AN: 152152 Hom.: 4088 Cov.: 32 AF XY: 0.221 AC XY: 16408 AN XY: 74380

African (AFR) AF: 0.330 AC: 13688 AN: 41496

American (AMR) AF: 0.246 AC: 3763 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 500 AN: 3472

East Asian (EAS) AF: 0.292 AC: 1508 AN: 5158

South Asian (SAS) AF: 0.274 AC: 1323 AN: 4824

European-Finnish (FIN) AF: 0.164 AC: 1735 AN: 10594

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9736 AN: 68002

Other (OTH) AF: 0.195 AC: 412 AN: 2110

Alfa AF: 0.205 Hom.: 2697

Bravo AF: 0.231

Asia WGS AF: 0.270 AC: 937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.71
PhyloP100		0.21
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: rs6693017; hg19: chr1-220977333;