Genetic Variant MTARC1:p.Thr165Ser (chr1-220796686-A-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.493A>T(p.Thr165Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 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:

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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=0.17480701).

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.493A>T	p.Thr165Ser	missense	Exon 3 of 7	NP_073583.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MTARC1	ENST00000366910.10	TSL:1 MANE Select	c.493A>T	p.Thr165Ser	missense	Exon 3 of 7	ENSP00000355877.5
ENSG00000286231	ENST00000651706.1		n.448A>T		non_coding_transcript_exon	Exon 3 of 9	ENSP00000499157.1
MTARC1	ENST00000694919.1		c.493A>T	p.Thr165Ser	missense	Exon 3 of 8	ENSP00000511594.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725884

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33296

American (AMR)

AF:

0.00

AC:

AN:

44266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26074

East Asian (EAS)

AF:

0.00

AC:

AN:

39414

South Asian (SAS)

AF:

0.00

AC:

AN:

85702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110950

Other (OTH)

AF:

0.00

AC:

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0069

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.77

M_CAP

Benign

0.013

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

3.9

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.10

REVEL

Benign

0.099

Sift

Benign

0.066

Sift4G

Uncertain

0.020

Polyphen

0.0030

Vest4

0.12

MutPred

0.59

Gain of catalytic residue at T165 (P = 0.0814)

MVP

0.18

MPC

0.15

ClinPred

0.32

GERP RS

3.9

PromoterAI

0.096

Neutral

(source)

Varity_R

0.047

gMVP

0.32

Mutation Taster

=91/9

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over