Variant 1-220780182-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000366913.8(MTARC2):c.827C>T(p.Thr276Met) variant causes a missense change. The variant allele was found at a frequency of 0.000209 in 1,612,614 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 2 hom. )

Consequence

MTARC2
ENST00000366913.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.23

Variant links:

Genes affected

MTARC2 (HGNC:26064): (mitochondrial amidoxime reducing component 2) The protein encoded by this gene is an enzyme found in the outer mitochondrial membrane that reduces N-hydroxylated substrates. The encoded protein uses molybdenum as a cofactor and cytochrome b5 type B and NADH cytochrome b5 reductase as accessory proteins. One type of substrate used is N-hydroxylated nucleotide base analogues, which can be toxic to a cell. Other substrates include N(omega)-hydroxy-L-arginine (NOHA) and amidoxime prodrugs, which are activated by the encoded enzyme. Multiple transcript variants encoding the different isoforms have been found for this gene. [provided by RefSeq, Sep 2016]

MTARC2 links:

MTARC2 (HGNC:):

MTARC2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTARC2	NM_017898.5 linkuse as main transcript	c.827C>T	p.Thr276Met	missense_variant	6/8	ENST00000366913.8	NP_060368.2	Q969Z3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MTARC2	ENST00000366913.8 linkuse as main transcript	c.827C>T	p.Thr276Met	missense_variant	6/8	1	NM_017898.5	ENSP00000355880.3	Q969Z3-1
MTARC2	ENST00000359316.6 linkuse as main transcript	c.751-3737C>T		intron_variant		1		ENSP00000352266.2	Q969Z3-2
MTARC2	ENST00000472447.1 linkuse as main transcript	n.221C>T		non_coding_transcript_exon_variant	1/3	2
MTARC2	ENST00000425560.1 linkuse as main transcript	c.*99C>T		downstream_gene_variant		3		ENSP00000416442.1	X1WI34

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000352

AC:

AN:

249834

Hom.:

AF XY:

0.000333

AC XY:

AN XY:

135104

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000689

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.000823

GnomAD4 exome

AF:

0.000211

AC:

308

AN:

1460414

Hom.:

Cov.:

AF XY:

0.000222

AC XY:

161

AN XY:

726576

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000895

Gnomad4 FIN exome

AF:

0.00172

Gnomad4 NFE exome

AF:

0.000110

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000191

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000149

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.000354

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.827C>T (p.T276M) alteration is located in exon 6 (coding exon 6) of the MARC2 gene. This alteration results from a C to T substitution at nucleotide position 827, causing the threonine (T) at amino acid position 276 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.89

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.55

MetaSVM

Benign

-0.45

MutationAssessor

Pathogenic

3.8

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-5.7

REVEL

Uncertain

0.38

Sift

Benign

0.045

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.90

MVP

0.68

MPC

0.93

ClinPred

0.29

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.20

Position offset: -14

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