chr1-220796686-A-G

Variant names:

• chr1-220796686-A-G
• rs2642438
• NM_022746.4:c.493A>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.493A>G​(p.Thr165Ala) variant causes a missense change. The variant allele was found at a frequency of 0.726 in 1,611,280 control chromosomes in the GnomAD database, including 426,929 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.78 (46648 hom., cov: 33)
  • Exomes 𝑓: 0.72 (380281 hom.)
• Consequence: MTARC1 NM_022746.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91
• Publications: 153 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 (MetaRNN=2.3516218E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022746.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTARC1	NM_022746.4	MANE Select	c.493A>G	p.Thr165Ala	missense	Exon 3 of 7	NP_073583.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTARC1	ENST00000366910.10	TSL:1 MANE Select	c.493A>G	p.Thr165Ala	missense	Exon 3 of 7	ENSP00000355877.5
	ENSG00000286231	ENST00000651706.1		n.448A>G		non_coding_transcript_exon	Exon 3 of 9	ENSP00000499157.1
	MTARC1	ENST00000694919.1		c.493A>G	p.Thr165Ala	missense	Exon 3 of 8	ENSP00000511594.1

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118154 AN: 152082 Hom.: 46595 Cov.: 33

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.756

GnomAD2 exomes AF: 0.752 AC: 186349 AN: 247726 AF XY: 0.745

Gnomad AFR exome AF: 0.924

Gnomad AMR exome AF: 0.827

Gnomad ASJ exome AF: 0.678

Gnomad EAS exome AF: 0.793

Gnomad FIN exome AF: 0.716

Gnomad NFE exome AF: 0.708

Gnomad OTH exome AF: 0.730

GnomAD4 exome AF: 0.720 AC: 1050848 AN: 1459080 Hom.: 380281 Cov.: 63 AF XY: 0.720 AC XY: 522454 AN XY: 725850

African (AFR) AF: 0.923 AC: 30730 AN: 33294

American (AMR) AF: 0.821 AC: 36349 AN: 44254

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 17652 AN: 26070

East Asian (EAS) AF: 0.812 AC: 31991 AN: 39406

South Asian (SAS) AF: 0.769 AC: 65902 AN: 85690

European-Finnish (FIN) AF: 0.717 AC: 38309 AN: 53396

Middle Eastern (MID) AF: 0.686 AC: 3952 AN: 5760

European-Non Finnish (NFE) AF: 0.704 AC: 782444 AN: 1110916

Other (OTH) AF: 0.722 AC: 43519 AN: 60294

GnomAD4 genome AF: 0.777 AC: 118265 AN: 152200 Hom.: 46648 Cov.: 33 AF XY: 0.777 AC XY: 57834 AN XY: 74410

African (AFR) AF: 0.917 AC: 38088 AN: 41542

American (AMR) AF: 0.779 AC: 11913 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2345 AN: 3468

East Asian (EAS) AF: 0.784 AC: 4053 AN: 5172

South Asian (SAS) AF: 0.778 AC: 3752 AN: 4824

European-Finnish (FIN) AF: 0.705 AC: 7465 AN: 10594

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48096 AN: 67994

Other (OTH) AF: 0.756 AC: 1594 AN: 2108

Alfa AF: 0.739 Hom.: 36108

Bravo AF: 0.794

TwinsUK AF: 0.710 AC: 2631

ALSPAC AF: 0.696 AC: 2681

ESP6500AA AF: 0.920 AC: 4053

ESP6500EA AF: 0.703 AC: 6048

ExAC AF: 0.754 AC: 91526

Asia WGS AF: 0.758 AC: 2639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.037
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.1
DANN	Benign	0.23
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0000023	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.6	N
PhyloP100		3.9
PrimateAI	Benign	0.40	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.046
MPC		0.16
ClinPred		0.0059	T
GERP RS		3.9
PromoterAI		0.096	Neutral
Varity_R		0.038
gMVP		0.28
Mutation Taster		=93/7	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: rs2642438; hg19: chr1-220970028; COSMIC: COSV107453139; COSMIC: COSV107453139;