Variant 1-220796753-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_022746.4(MTARC1):c.560T>A(p.Met187Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0092 in 1,612,844 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0062 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0095 ( 72 hom. )

Consequence

MTARC1
NM_022746.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.94

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0072243214).

BP6

Variant 1-220796753-T-A is Benign according to our data. Variant chr1-220796753-T-A is described in ClinVar as [Benign]. Clinvar id is 708513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTARC1	NM_022746.4 linkuse as main transcript	c.560T>A	p.Met187Lys	missense_variant	3/7	ENST00000366910.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTARC1	ENST00000366910.10 linkuse as main transcript	c.560T>A	p.Met187Lys	missense_variant	3/7	1	NM_022746.4	P1	Q5VT66-1

Frequencies

GnomAD3 genomes

AF:

0.00618

AC:

940

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00697

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00728

AC:

1813

AN:

249198

Hom.:

AF XY:

0.00734

AC XY:

989

AN XY:

134804

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00204

Gnomad ASJ exome

AF:

0.00458

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00442

Gnomad FIN exome

AF:

0.00817

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.00631

GnomAD4 exome

AF:

0.00951

AC:

13891

AN:

1460562

Hom.:

Cov.:

AF XY:

0.00932

AC XY:

6773

AN XY:

726584

show subpopulations

Gnomad4 AFR exome

AF:

0.00141

Gnomad4 AMR exome

AF:

0.00193

Gnomad4 ASJ exome

AF:

0.00463

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00448

Gnomad4 FIN exome

AF:

0.00983

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.00920

GnomAD4 genome

AF:

0.00617

AC:

940

AN:

152282

Hom.:

Cov.:

AF XY:

0.00576

AC XY:

429

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00697

Gnomad4 NFE

AF:

0.0104

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00806

Hom.:

Bravo

AF:

0.00588

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0112

AC:

ExAC

AF:

0.00829

AC:

1007

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00829

EpiControl

AF:

0.00959

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 11, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	MTARC1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.087

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0072

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.6

REVEL

Benign

0.15

Sift

Uncertain

0.010

Sift4G

Benign

0.13

Polyphen

0.98

Vest4

0.72

MVP

0.53

MPC

0.30

ClinPred

0.062

GERP RS

3.7

Varity_R

0.65

gMVP

0.73

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over