Genetic Variant MTARC1:p.Arg90Gln (chr1-220787213-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_022746.4(MTARC1):c.269G>A(p.Arg90Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 1,418,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

MTARC1
NM_022746.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

Publications

1 publications found

Variant links:

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]

MTARC1 links:

ENSG00000286231 (HGNC:):

ENSG00000286231 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTARC1	NM_022746.4 link	c.269G>A	p.Arg90Gln	missense_variant	Exon 1 of 7	ENST00000366910.10	NP_073583.3	Q5VT66-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTARC1	ENST00000366910.10 link	c.269G>A	p.Arg90Gln	missense_variant	Exon 1 of 7	1	NM_022746.4	ENSP00000355877.5		Q5VT66-1
ENSG00000286231	ENST00000651706.1 link	n.224G>A		non_coding_transcript_exon_variant	Exon 1 of 9			ENSP00000499157.1		A0A494C1P3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000173

AC:

AN:

173406

AF XY:

0.0000213

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000282

AC:

AN:

1418130

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

701946

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32112

American (AMR)

AF:

0.0000764

AC:

AN:

39286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25288

East Asian (EAS)

AF:

0.00

AC:

AN:

36748

South Asian (SAS)

AF:

0.00

AC:

AN:

80914

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5366

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091206

Other (OTH)

AF:

0.0000171

AC:

AN:

58606

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000256

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 17, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.269G>A (p.R90Q) alteration is located in exon 1 (coding exon 1) of the MARC1 gene. This alteration results from a G to A substitution at nucleotide position 269, causing the arginine (R) at amino acid position 90 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

Eigen

Benign

-0.011

Eigen_PC

Benign

0.0021

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

3.4

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.6

REVEL

Benign

0.070

Sift

Benign

0.10

Sift4G

Benign

0.14

Polyphen

0.95

Vest4

0.13

MutPred

0.63

Loss of MoRF binding (P = 0.0458);

MVP

0.44

MPC

0.22

ClinPred

0.62

GERP RS

4.0

PromoterAI

0.023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.52

Mutation Taster

=78/22

polymorphism

(source)

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

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1-220787213-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over