10-119172416-C-A

Position:

chr10-119172416-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP3BP4_StrongBP6_ModerateBS1BS2

The NM_006793.5(PRDX3):c.517G>T(p.Gly173Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00665 in 1,613,992 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 53 hom. )

Consequence

PRDX3
NM_006793.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.85

Variant links:

Genes affected

PRDX3 (HGNC:9354): (peroxiredoxin 3) This gene encodes a mitochondrial protein with antioxidant function. The protein is similar to the C22 subunit of Salmonella typhimurium alkylhydroperoxide reductase, and it can rescue bacterial resistance to alkylhydroperoxide in E. coli that lack the C22 subunit. The human and mouse genes are highly conserved, and they map to the regions syntenic between mouse and human chromosomes. Sequence comparisons with recently cloned mammalian homologs suggest that these genes consist of a family that is responsible for the regulation of cellular proliferation, differentiation and antioxidant functions. This family member can protect cells from oxidative stress, and it can promote cell survival in prostate cancer. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 1, 3, 13 and 22. [provided by RefSeq, Oct 2014]

PRDX3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: BayesDel_noAF, Cadd, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate, PrimateAI, PROVEAN [when BayesDel_addAF, max_spliceai, M_CAP, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.024121523).

BP6

Variant 10-119172416-C-A is Benign according to our data. Variant chr10-119172416-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640876.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00506 (771/152294) while in subpopulation AMR AF= 0.0101 (155/15300). AF 95% confidence interval is 0.00883. There are 4 homozygotes in gnomad4. There are 376 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDX3	NM_006793.5 linkuse as main transcript	c.517G>T	p.Gly173Cys	missense_variant	5/7	ENST00000298510.4	NP_006784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDX3	ENST00000298510.4 linkuse as main transcript	c.517G>T	p.Gly173Cys	missense_variant	5/7	1	NM_006793.5	ENSP00000298510	P1	P30048-1

Frequencies

GnomAD3 genomes

AF:

0.00507

AC:

772

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00733

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00514

AC:

1292

AN:

251486

Hom.:

AF XY:

0.00541

AC XY:

735

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00402

Gnomad ASJ exome

AF:

0.00486

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00425

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.00762

Gnomad OTH exome

AF:

0.00814

GnomAD4 exome

AF:

0.00681

AC:

9960

AN:

1461698

Hom.:

Cov.:

AF XY:

0.00676

AC XY:

4918

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00423

Gnomad4 ASJ exome

AF:

0.00471

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00452

Gnomad4 FIN exome

AF:

0.00170

Gnomad4 NFE exome

AF:

0.00782

Gnomad4 OTH exome

AF:

0.00652

GnomAD4 genome

AF:

0.00506

AC:

771

AN:

152294

Hom.:

Cov.:

AF XY:

0.00505

AC XY:

376

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00734

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00686

Hom.:

Bravo

AF:

0.00592

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00942

AC:

ExAC

AF:

0.00518

AC:

629

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00938

EpiControl

AF:

0.00723

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

PRDX3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.97

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.034

MetaRNN

Benign

0.024

MetaSVM

Uncertain

0.10

MutationAssessor

Pathogenic

5.0

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-7.9

REVEL

Uncertain

0.64

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.84

MVP

0.79

MPC

0.43

ClinPred

0.17

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.95

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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