Genetic Variant MTARC1:p.Thr165Ala (chr1-220796686-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022746.4(MTARC1):c.493A>G(p.Thr165Ala) variant causes a missense change. The variant allele was found at a frequency of 0.726 in 1,611,280 control chromosomes in the GnomAD database, including 426,929 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.78 ( 46648 hom., cov: 33)

Exomes 𝑓: 0.72 ( 380281 hom. )

Consequence

MTARC1
NM_022746.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.91

Publications

153 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3516218E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTARC1	NM_022746.4 link	c.493A>G	p.Thr165Ala	missense_variant	Exon 3 of 7	ENST00000366910.10	NP_073583.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTARC1	ENST00000366910.10 link	c.493A>G	p.Thr165Ala	missense_variant	Exon 3 of 7	1	NM_022746.4	ENSP00000355877.5
ENSG00000286231	ENST00000651706.1 link	n.448A>G		non_coding_transcript_exon_variant	Exon 3 of 9			ENSP00000499157.1

Frequencies

GnomAD3 genomes

AF:

0.777

AC:

118154

AN:

152082

Hom.:

46595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.917

Gnomad AMI

AF:

0.818

Gnomad AMR

AF:

0.779

Gnomad ASJ

AF:

0.676

Gnomad EAS

AF:

0.784

Gnomad SAS

AF:

0.779

Gnomad FIN

AF:

0.705

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.707

Gnomad OTH

AF:

0.756

GnomAD2 exomes

AF:

0.752

AC:

186349

AN:

247726

AF XY:

0.745

show subpopulations

Gnomad AFR exome

AF:

0.924

Gnomad AMR exome

AF:

0.827

Gnomad ASJ exome

AF:

0.678

Gnomad EAS exome

AF:

0.793

Gnomad FIN exome

AF:

0.716

Gnomad NFE exome

AF:

0.708

Gnomad OTH exome

AF:

0.730

GnomAD4 exome

AF:

0.720

AC:

1050848

AN:

1459080

Hom.:

380281

Cov.:

AF XY:

0.720

AC XY:

522454

AN XY:

725850

show subpopulations

African (AFR)

AF:

0.923

AC:

30730

AN:

33294

American (AMR)

AF:

0.821

AC:

36349

AN:

44254

Ashkenazi Jewish (ASJ)

AF:

0.677

AC:

17652

AN:

26070

East Asian (EAS)

AF:

0.812

AC:

31991

AN:

39406

South Asian (SAS)

AF:

0.769

AC:

65902

AN:

85690

European-Finnish (FIN)

AF:

0.717

AC:

38309

AN:

53396

Middle Eastern (MID)

AF:

0.686

AC:

3952

AN:

5760

European-Non Finnish (NFE)

AF:

0.704

AC:

782444

AN:

1110916

Other (OTH)

AF:

0.722

AC:

43519

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

16204

32408

48612

64816

81020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19778

39556

59334

79112

98890

<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:

0.777

AC:

118265

AN:

152200

Hom.:

46648

Cov.:

AF XY:

0.777

AC XY:

57834

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.917

AC:

38088

AN:

41542

American (AMR)

AF:

0.779

AC:

11913

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.676

AC:

2345

AN:

3468

East Asian (EAS)

AF:

0.784

AC:

4053

AN:

5172

South Asian (SAS)

AF:

0.778

AC:

3752

AN:

4824

European-Finnish (FIN)

AF:

0.705

AC:

7465

AN:

10594

Middle Eastern (MID)

AF:

0.724

AC:

213

AN:

294

European-Non Finnish (NFE)

AF:

0.707

AC:

48096

AN:

67994

Other (OTH)

AF:

0.756

AC:

1594

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1336

2672

4009

5345

6681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

858

1716

2574

3432

4290

<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:

0.739

Hom.:

36108

Bravo

AF:

0.794

TwinsUK

AF:

0.710

AC:

2631

ALSPAC

AF:

0.696

AC:

2681

ESP6500AA

AF:

0.920

AC:

4053

ESP6500EA

AF:

0.703

AC:

6048

ExAC

AF:

0.754

AC:

91526

Asia WGS

AF:

0.758

AC:

2639

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.037

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.1

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.0021

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0000024

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.6

PhyloP100

3.9

PrimateAI

Benign

0.40

PROVEAN

Benign

2.4

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.046

MPC

0.16

ClinPred

0.0059

GERP RS

3.9

PromoterAI

0.096

Neutral

(source)

Varity_R

0.038

gMVP

0.28

Mutation Taster

=93/7

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over