chr1-220797997-T-A

Variant names:

• chr1-220797997-T-A
• rs3738178
• NM_022746.4:c.736T>A

Variant summary

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

The NM_022746.4(MTARC1):​c.736T>A​(p.Cys246Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0093 in 1,614,246 control chromosomes in the GnomAD database, including 839 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (98 hom., cov: 33)
  • Exomes 𝑓: 0.0087 (741 hom.)
• Consequence: MTARC1 NM_022746.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.28
• Publications: 13 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=0.0026366115).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0825 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.736T>A	p.Cys246Ser	missense	Exon 4 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.736T>A	p.Cys246Ser	missense	Exon 4 of 7	ENSP00000355877.5
	ENSG00000286231	ENST00000651706.1		n.691T>A		non_coding_transcript_exon	Exon 4 of 9	ENSP00000499157.1
	MTARC1	ENST00000694919.1		c.736T>A	p.Cys246Ser	missense	Exon 4 of 8	ENSP00000511594.1

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2346 AN: 152244 Hom.: 96 Cov.: 33

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0858

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0613

Gnomad SAS AF: 0.0136

Gnomad FIN AF: 0.00480

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.0229

GnomAD2 exomes AF: 0.0296 AC: 7445 AN: 251478 AF XY: 0.0242

Gnomad AFR exome AF: 0.0129

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.0519

Gnomad FIN exome AF: 0.00517

Gnomad NFE exome AF: 0.000853

Gnomad OTH exome AF: 0.0239

GnomAD4 exome AF: 0.00866 AC: 12663 AN: 1461884 Hom.: 741 Cov.: 31 AF XY: 0.00814 AC XY: 5923 AN XY: 727242

African (AFR) AF: 0.0128 AC: 427 AN: 33480

American (AMR) AF: 0.150 AC: 6704 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 27 AN: 26134

East Asian (EAS) AF: 0.0733 AC: 2908 AN: 39698

South Asian (SAS) AF: 0.0142 AC: 1227 AN: 86258

European-Finnish (FIN) AF: 0.00547 AC: 292 AN: 53420

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5768

European-Non Finnish (NFE) AF: 0.000450 AC: 500 AN: 1112010

Other (OTH) AF: 0.00937 AC: 566 AN: 60396

GnomAD4 genome AF: 0.0154 AC: 2353 AN: 152362 Hom.: 98 Cov.: 33 AF XY: 0.0167 AC XY: 1244 AN XY: 74516

African (AFR) AF: 0.0116 AC: 483 AN: 41584

American (AMR) AF: 0.0864 AC: 1322 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.0611 AC: 317 AN: 5188

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4832

European-Finnish (FIN) AF: 0.00480 AC: 51 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000897 AC: 61 AN: 68030

Other (OTH) AF: 0.0222 AC: 47 AN: 2116

Alfa AF: 0.00518 Hom.: 20

Bravo AF: 0.0244

ESP6500AA AF: 0.0129 AC: 57

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.0243 AC: 2952

Asia WGS AF: 0.0500 AC: 173 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Benign	0.058
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
PhyloP100		6.3
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-9.7	D
REVEL	Benign	0.29
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.044	D
Polyphen		0.99	D
Vest4		0.31
MutPred		0.25		Loss of stability (P = 0.0223)
MPC		0.26
ClinPred		0.12	T
GERP RS		4.9
Varity_R		0.80
gMVP		0.66
Mutation Taster		=81/19	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: rs3738178; hg19: chr1-220971339; COSMIC: COSV107453140;