chr1-220791501-G-C

Position:

• chr1-220791501-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000366910.10(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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0023 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (80 hom.)
• Consequence: MTARC1 ENST00000366910.10 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.42

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTARC1	NM_022746.4	c.286G>C	p.Val96Leu	missense_variant	2/7	ENST00000366910.10	NP_073583.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTARC1	ENST00000366910.10	c.286G>C	p.Val96Leu	missense_variant	2/7	1	NM_022746.4	ENSP00000355877.5
ENSG00000286231	ENST00000651706.1	n.241G>C		non_coding_transcript_exon_variant	2/9			ENSP00000499157.1

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

GnomAD3 exomes AF: 0.00507 AC: 1272 AN: 250790 Hom.: 40 AF XY: 0.00485 AC XY: 657 AN XY: 135564

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 SAS exome AF: 0.00203

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

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.000192

Gnomad4 EAS exome AF: 0.0573

Gnomad4 SAS exome AF: 0.00194

Gnomad4 FIN exome AF: 0.000243

Gnomad4 NFE exome AF: 0.0000486

Gnomad4 OTH exome AF: 0.00278

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

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0587

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00189

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	D
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
Varity_R		0.72
gMVP		0.65

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: rs12023067; hg19: chr1-220964843; COSMIC: COSV65055974; COSMIC: COSV65055974;