Variant rs3738178 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022746.4(MTARC1):c.736T>A(p.Cys246Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0093 in 1,614,246 control chromosomes in the GnomAD database, including 839 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

Frequency

Genomes: 𝑓 0.015 ( 98 hom., cov: 33)

Exomes 𝑓: 0.0087 ( 741 hom. )

Consequence

MTARC1
NM_022746.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.28

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026366115).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTARC1	NM_022746.4 linkuse as main transcript	c.736T>A	p.Cys246Ser	missense_variant	4/7	ENST00000366910.10	NP_073583.3	Q5VT66-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTARC1	ENST00000366910.10 linkuse as main transcript	c.736T>A	p.Cys246Ser	missense_variant	4/7	1	NM_022746.4	ENSP00000355877.5		Q5VT66-1
ENSG00000286231	ENST00000651706.1 linkuse as main transcript	n.691T>A		non_coding_transcript_exon_variant	4/9			ENSP00000499157.1		A0A494C1P3

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2346

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0858

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0613

Gnomad SAS

AF:

0.0136

Gnomad FIN

AF:

0.00480

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.0229

GnomAD3 exomes

AF:

0.0296

AC:

7445

AN:

251478

Hom.:

519

AF XY:

0.0242

AC XY:

3285

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0129

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.0519

Gnomad SAS exome

AF:

0.0161

Gnomad FIN exome

AF:

0.00517

Gnomad NFE exome

AF:

0.000853

Gnomad OTH exome

AF:

0.0239

GnomAD4 exome

AF:

0.00866

AC:

12663

AN:

1461884

Hom.:

741

Cov.:

AF XY:

0.00814

AC XY:

5923

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0128

Gnomad4 AMR exome

AF:

0.150

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.0733

Gnomad4 SAS exome

AF:

0.0142

Gnomad4 FIN exome

AF:

0.00547

Gnomad4 NFE exome

AF:

0.000450

Gnomad4 OTH exome

AF:

0.00937

GnomAD4 genome

AF:

0.0154

AC:

2353

AN:

152362

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

1244

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.0116

Gnomad4 AMR

AF:

0.0864

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.0611

Gnomad4 SAS

AF:

0.0137

Gnomad4 FIN

AF:

0.00480

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.00518

Hom.:

Bravo

AF:

0.0244

ESP6500AA

AF:

0.0129

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.0243

AC:

2952

Asia WGS

AF:

0.0500

AC:

173

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.056

T;T

Eigen

Benign

0.058

Eigen_PC

Benign

0.024

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.73

T;D

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

M;.

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-9.7

D;D

REVEL

Benign

0.29

Sift

Uncertain

0.0020

D;T

Sift4G

Uncertain

0.044

D;T

Polyphen

0.99

D;.

Vest4

0.31

MutPred

0.25

Loss of stability (P = 0.0223);.;

MPC

0.26

ClinPred

0.12

GERP RS

4.9

Varity_R

0.80

gMVP

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over