1-220791501-G-C

Variant names:

• chr1-220791501-G-C
• rs12023067
• NM_022746.4:c.286G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022746.4(MTARC1):​c.286G>C​(p.Val96Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,613,924 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (80 hom.)
• Consequence: MTARC1 NM_022746.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.42
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0051474273).
• BP6: Variant 1-220791501-G-C is Benign according to our data. Variant chr1-220791501-G-C is described in ClinVar as Benign. ClinVar VariationId is 773642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0533 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTARC1	NM_022746.4	MANE Select	c.286G>C	p.Val96Leu	missense	Exon 2 of 7	NP_073583.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTARC1	ENST00000366910.10	TSL:1 MANE Select	c.286G>C	p.Val96Leu	missense	Exon 2 of 7	ENSP00000355877.5	Q5VT66-1
	ENSG00000286231	ENST00000651706.1		n.241G>C		non_coding_transcript_exon	Exon 2 of 9	ENSP00000499157.1	A0A494C1P3
	MTARC1	ENST00000694918.1		c.-21G>C		5_prime_UTR_premature_start_codon_gain	Exon 3 of 8	ENSP00000511593.1	A0A8Q3SHL7

Frequencies

GnomAD3 genomes AF: 0.00234 AC: 356 AN: 152110 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0586

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00507 AC: 1272 AN: 250790 AF XY: 0.00485

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.000399

Gnomad EAS exome AF: 0.0636

Gnomad FIN exome AF: 0.000418

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00184 AC: 2688 AN: 1461696 Hom.: 80 Cov.: 31 AF XY: 0.00181 AC XY: 1313 AN XY: 727136

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000192 AC: 5 AN: 26084

East Asian (EAS) AF: 0.0573 AC: 2273 AN: 39694

South Asian (SAS) AF: 0.00194 AC: 167 AN: 86246

European-Finnish (FIN) AF: 0.000243 AC: 13 AN: 53398

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5764

European-Non Finnish (NFE) AF: 0.0000486 AC: 54 AN: 1111922

Other (OTH) AF: 0.00278 AC: 168 AN: 60388

GnomAD4 genome AF: 0.00234 AC: 356 AN: 152228 Hom.: 7 Cov.: 32 AF XY: 0.00263 AC XY: 196 AN XY: 74442

African (AFR) AF: 0.000241 AC: 10 AN: 41532

American (AMR) AF: 0.000392 AC: 6 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.0587 AC: 303 AN: 5158

South Asian (SAS) AF: 0.00415 AC: 20 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68010

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00200 Hom.: 9

Bravo AF: 0.00320

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.00517 AC: 628

Asia WGS AF: 0.0150 AC: 53 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.4
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.16
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.094	T
Polyphen		0.99	D
Vest4		0.47
MutPred		0.28		Loss of MoRF binding (P = 0.0912)
MVP		0.53
MPC		0.23
ClinPred		0.058	T
GERP RS		2.8
PromoterAI		0.012	Neutral
Varity_R		0.72
gMVP		0.65
Mutation Taster		=94/6	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: rs12023067; hg19: chr1-220964843; COSMIC: COSV65055974; COSMIC: COSV65055974;