rs6693017

chr1-220803991-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MTARC1	NM_022746.4	c.754-1061T>G		intron_variant		ENST00000366910.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTARC1	ENST00000366910.10	c.754-1061T>G		intron_variant		1	NM_022746.4	P1

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

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.195

Alfa AF: 0.167 Hom.: 696

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

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: rs6693017; hg19: chr1-220977333;