10-119168032-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006793.5(PRDX3):c.*448A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 159,848 control chromosomes in the GnomAD database, including 17,681 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 0.44 (16612 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1069 hom.)
• Consequence: PRDX3 NM_006793.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDX3	NM_006793.5	c.*448A>C		3_prime_UTR_variant	7/7	ENST00000298510.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDX3	ENST00000298510.4	c.*448A>C		3_prime_UTR_variant	7/7	1	NM_006793.5	P1
PRDX3	ENST00000494433.1			downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66230 AN: 152020 Hom.: 16606 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.465

GnomAD4 exome AF: 0.500 AC: 3853 AN: 7710 Hom.: 1069 Cov.: 0 AF XY: 0.497 AC XY: 1919 AN XY: 3860

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.437

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.260

Gnomad4 SAS exome AF: 0.484

Gnomad4 FIN exome AF: 0.582

Gnomad4 NFE exome AF: 0.506

Gnomad4 OTH exome AF: 0.498

GnomAD4 genome AF: 0.435 AC: 66232 AN: 152138 Hom.: 16612 Cov.: 33 AF XY: 0.439 AC XY: 32674 AN XY: 74370

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.464

Alfa AF: 0.514 Hom.: 25283

Bravo AF: 0.412

Asia WGS AF: 0.462 AC: 1603 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.60
Dann	Benign	0.34

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

LitVar

Other links and lift over

dbSNP: rs3377; hg19: chr10-120927544;