dbSNP rs11554923: PRDX3:p.Gly173Cys (chr10-119172416-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

corneal dystrophy, punctiform and polychromatic pre-descemet
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
spinocerebellar ataxia, autosomal recessive 32
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

PRDX3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006793.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRDX3	NM_006793.5	MANE Select	c.517G>T	p.Gly173Cys	missense	Exon 5 of 7	NP_006784.1	P30048-1
PRDX3	NM_001302272.2		c.517G>T	p.Gly173Cys	missense	Exon 5 of 6	NP_001289201.1
PRDX3	NR_126102.2		n.406G>T		non_coding_transcript_exon	Exon 4 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRDX3	ENST00000298510.4	TSL:1 MANE Select	c.517G>T	p.Gly173Cys	missense	Exon 5 of 7	ENSP00000298510.2	P30048-1
PRDX3	ENST00000865262.1		c.664G>T	p.Gly222Cys	missense	Exon 5 of 7	ENSP00000535321.1
PRDX3	ENST00000865257.1		c.550G>T	p.Gly184Cys	missense	Exon 5 of 7	ENSP00000535316.1

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

GnomAD2 exomes

AF:

0.00514

AC:

1292

AN:

251486

AF XY:

0.00541

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 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

African (AFR)

AF:

0.00111

AC:

AN:

33474

American (AMR)

AF:

0.00423

AC:

189

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00471

AC:

123

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00452

AC:

390

AN:

86254

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00763

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00782

AC:

8691

AN:

1111842

Other (OTH)

AF:

0.00652

AC:

394

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

467

934

1401

1868

2335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

340

680

1020

1360

1700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00506

AC:

771

AN:

152294

Hom.:

Cov.:

AF XY:

0.00505

AC XY:

376

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00116

AC:

AN:

41558

American (AMR)

AF:

0.0101

AC:

155

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00663

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00394

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00734

AC:

499

AN:

68030

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

123

164

205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00647

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

(source)

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

PhyloP100

7.8

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

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over