rs12033808

Variant names:

• chr1-220798492-T-C
• rs12033808
• NM_022746.4:c.753+478T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.83).
• 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 rank	MANE	Protein	UniProt
MTARC1	NM_022746.4	c.753+478T>C		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.753+478T>C		intron_variant	Intron 4 of 6	1	NM_022746.4	ENSP00000355877.5
ENSG00000286231	ENST00000651706.1	n.708+478T>C		intron_variant	Intron 4 of 8			ENSP00000499157.1

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

African (AFR) AF: 0.0536 AC: 846 AN: 15786

American (AMR) AF: 0.00610 AC: 6 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.00951 AC: 49 AN: 5152

East Asian (EAS) AF: 0.0595 AC: 216 AN: 3630

South Asian (SAS) AF: 0.0655 AC: 1078 AN: 16456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 276

Middle Eastern (MID) AF: 0.0198 AC: 32 AN: 1620

European-Non Finnish (NFE) AF: 0.00413 AC: 3145 AN: 761902

Other (OTH) AF: 0.0171 AC: 468 AN: 27298

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

African (AFR) AF: 0.0520 AC: 2161 AN: 41578

American (AMR) AF: 0.00915 AC: 140 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3468

East Asian (EAS) AF: 0.0634 AC: 329 AN: 5190

South Asian (SAS) AF: 0.0636 AC: 307 AN: 4828

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00440 AC: 299 AN: 68026

Other (OTH) AF: 0.0199 AC: 42 AN: 2114

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
PhyloP100		-0.68
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: rs12033808; hg19: chr1-220971834;