rs12033808

chr1-220798492-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022746.4(MTARC1):c.753+478T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00929 in 985,432 control chromosomes in the GnomAD database, including 166 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 0.022 (67 hom., cov: 33)
  • Exomes 𝑓: 0.0070 (99 hom.)
• Consequence: MTARC1 NM_022746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTARC1	NM_022746.4	c.753+478T>C		intron_variant		ENST00000366910.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTARC1	ENST00000366910.10	c.753+478T>C		intron_variant		1	NM_022746.4	P1

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3314 AN: 152210 Hom.: 67 Cov.: 33

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00917

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.0632

Gnomad SAS AF: 0.0644

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00439

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.00701 AC: 5840 AN: 833104 Hom.: 99 Cov.: 30 AF XY: 0.00700 AC XY: 2694 AN XY: 384712

Gnomad4 AFR exome AF: 0.0536

Gnomad4 AMR exome AF: 0.00610

Gnomad4 ASJ exome AF: 0.00951

Gnomad4 EAS exome AF: 0.0595

Gnomad4 SAS exome AF: 0.0655

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00413

Gnomad4 OTH exome AF: 0.0171

GnomAD4 genome AF: 0.0218 AC: 3319 AN: 152328 Hom.: 67 Cov.: 33 AF XY: 0.0221 AC XY: 1643 AN XY: 74502

Gnomad4 AFR AF: 0.0520

Gnomad4 AMR AF: 0.00915

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.0634

Gnomad4 SAS AF: 0.0636

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00440

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0138 Hom.: 7

Bravo AF: 0.0234

Asia WGS AF: 0.0550 AC: 195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.76
Dann	Benign	0.78

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: rs12033808; hg19: chr1-220971834;