NM_017898.5:c.273-1445G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017898.5(MTARC2):​c.273-1445G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,158 control chromosomes in the GnomAD database, including 1,762 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.

Frequency

Genomes: 𝑓 0.13 ( 1762 hom., cov: 32)

Consequence

MTARC2
NM_017898.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Publications

2 publications found
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTARC2NM_017898.5 linkc.273-1445G>A intron_variant Intron 1 of 7 ENST00000366913.8 NP_060368.2 Q969Z3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTARC2ENST00000366913.8 linkc.273-1445G>A intron_variant Intron 1 of 7 1 NM_017898.5 ENSP00000355880.3 Q969Z3-1
MTARC2ENST00000359316.6 linkc.273-1445G>A intron_variant Intron 1 of 4 1 ENSP00000352266.2 Q969Z3-2
MTARC2ENST00000469583.1 linkn.273-866G>A intron_variant Intron 1 of 2 3 ENSP00000435450.1 F6V6Z1

Frequencies

GnomAD3 genomes
AF:
0.131
AC:
19974
AN:
152040
Hom.:
1754
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0482
Gnomad AMI
AF:
0.0658
Gnomad AMR
AF:
0.237
Gnomad ASJ
AF:
0.163
Gnomad EAS
AF:
0.248
Gnomad SAS
AF:
0.186
Gnomad FIN
AF:
0.175
Gnomad MID
AF:
0.180
Gnomad NFE
AF:
0.137
Gnomad OTH
AF:
0.144
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.131
AC:
19992
AN:
152158
Hom.:
1762
Cov.:
32
AF XY:
0.136
AC XY:
10134
AN XY:
74394
show subpopulations
African (AFR)
AF:
0.0483
AC:
2006
AN:
41528
American (AMR)
AF:
0.238
AC:
3635
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.163
AC:
567
AN:
3472
East Asian (EAS)
AF:
0.248
AC:
1278
AN:
5146
South Asian (SAS)
AF:
0.186
AC:
896
AN:
4820
European-Finnish (FIN)
AF:
0.175
AC:
1858
AN:
10608
Middle Eastern (MID)
AF:
0.180
AC:
53
AN:
294
European-Non Finnish (NFE)
AF:
0.137
AC:
9340
AN:
67982
Other (OTH)
AF:
0.142
AC:
299
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
853
1707
2560
3414
4267
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
230
460
690
920
1150
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.143
Hom.:
919
Bravo
AF:
0.139
Asia WGS
AF:
0.198
AC:
690
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
3.5
DANN
Benign
0.75
PhyloP100
1.0
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12407624; hg19: chr1-220926844; API