10-119172416-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP3 BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.85

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]

ACMG classification

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 GnomAd at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDX3	NM_006793.5	c.517G>T	p.Gly173Cys	missense_variant	5/7	ENST00000298510.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDX3	ENST00000298510.4	c.517G>T	p.Gly173Cys	missense_variant	5/7	1	NM_006793.5	P1

Frequencies

GnomAD3 genomes AF: 0.00507 AC: 772 AN: 152176 Hom.: 4 Cov.: 32

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.: 11 AF XY: 0.00541 AC XY: 735 AN XY: 135914

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.: 53 Cov.: 30 AF XY: 0.00676 AC XY: 4918 AN XY: 727164

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.: 4 Cov.: 32 AF XY: 0.00505 AC XY: 376 AN XY: 74468

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.: 14

Bravo AF: 0.00592

TwinsUK AF: 0.00863 AC: 32

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.00942 AC: 81

ExAC AF: 0.00518 AC: 629

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00938

EpiControl AF: 0.00723

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Pathogenic	0.15
Cadd	Pathogenic	28
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.97
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.024	T
MetaSVM	Uncertain	0.10	D
MutationAssessor	Pathogenic	5.0	H
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-7.9	D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MVP		0.79
MPC		0.43
ClinPred		0.17	T
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

Other links and lift over

dbSNP: rs11554923; hg19: chr10-120931928; COSMIC: COSV100045501; COSMIC: COSV100045501;