dbSNP rs1277242590: MTARC1:p.Arg42Cys (chr1-220787068-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022746.4(MTARC1):c.124C>T(p.Arg42Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000083 in 1,444,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

MTARC1
NM_022746.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00500

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14969456).

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.124C>T	p.Arg42Cys	missense	Exon 1 of 7	NP_073583.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTARC1	ENST00000366910.10	TSL:1 MANE Select	c.124C>T	p.Arg42Cys	missense	Exon 1 of 7	ENSP00000355877.5	Q5VT66-1
ENSG00000286231	ENST00000651706.1		n.79C>T		non_coding_transcript_exon	Exon 1 of 9	ENSP00000499157.1	A0A494C1P3
MTARC1	ENST00000694919.1		c.124C>T	p.Arg42Cys	missense	Exon 1 of 8	ENSP00000511594.1	A0A8Q3SHG3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000396

AC:

AN:

50568

AF XY:

0.0000332

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00169

GnomAD4 exome

AF:

0.00000696

AC:

AN:

1292922

Hom.:

Cov.:

AF XY:

0.00000785

AC XY:

AN XY:

637130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24284

American (AMR)

AF:

0.0000701

AC:

AN:

14260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20256

East Asian (EAS)

AF:

0.00

AC:

AN:

28548

South Asian (SAS)

AF:

0.0000151

AC:

AN:

66108

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3688

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1040384

Other (OTH)

AF:

0.000132

AC:

AN:

52860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.614

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152012

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41418

American (AMR)

AF:

0.000131

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10538

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000302

Asia WGS

AF:

0.000869

AC:

AN:

3468

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.59

M_CAP

Pathogenic

0.51

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.1

PhyloP100

0.0050

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.8

REVEL

Benign

0.045

Sift

Benign

0.093

Sift4G

Benign

0.17

Polyphen

0.013

Vest4

0.12

MutPred

0.49

Loss of loop (P = 0.0073)

MVP

0.18

MPC

0.52

ClinPred

0.57

GERP RS

-0.44

PromoterAI

0.0079

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.062

gMVP

0.66

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over