Genetic Variant MTARC1:p.Val13Ile (chr1-220786981-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022746.4(MTARC1):c.37G>A(p.Val13Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000089 in 1,123,112 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.9e-7 ( 0 hom. )

Consequence

MTARC1
NM_022746.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.312

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053827524).

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.37G>A	p.Val13Ile	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.37G>A	p.Val13Ile	missense	Exon 1 of 7	ENSP00000355877.5	Q5VT66-1
MTARC1	ENST00000694919.1		c.37G>A	p.Val13Ile	missense	Exon 1 of 8	ENSP00000511594.1	A0A8Q3SHG3
MTARC1	ENST00000865600.1		c.37G>A	p.Val13Ile	missense	Exon 1 of 6	ENSP00000535659.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.90e-7

AC:

AN:

1123112

Hom.:

Cov.:

AF XY:

0.00000185

AC XY:

AN XY:

539356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22910

American (AMR)

AF:

0.00

AC:

AN:

8468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14554

East Asian (EAS)

AF:

0.00

AC:

AN:

26582

South Asian (SAS)

AF:

0.00

AC:

AN:

27240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3016

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

949072

Other (OTH)

AF:

0.0000221

AC:

AN:

45148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Cov.:

Asia WGS

AF:

0.000290

AC:

AN:

3462

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

0.12

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.1

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0056

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.57

M_CAP

Benign

0.017

MetaRNN

Benign

0.054

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PhyloP100

-0.31

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.27

REVEL

Benign

0.027

Sift

Benign

0.14

Sift4G

Benign

0.13

Polyphen

0.0

Vest4

0.051

MutPred

0.34

Gain of helix (P = 0.0854)

MVP

0.072

MPC

0.13

ClinPred

0.062

GERP RS

0.92

PromoterAI

-0.24

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.043

gMVP

0.19

Mutation Taster

=94/6

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over