10-119169426-C-T

Variant summary

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

The NM_006793.5(PRDX3):c.552-84G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,143,268 control chromosomes in the GnomAD database, including 46,059 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 0.29 (6659 hom., cov: 31)
  • Exomes 𝑓: 0.28 (39400 hom.)
• Consequence: PRDX3 NM_006793.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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 (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDX3	NM_006793.5	c.552-84G>A		intron_variant		ENST00000298510.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDX3	ENST00000298510.4	c.552-84G>A		intron_variant		1	NM_006793.5	P1
PRDX3	ENST00000494433.1	n.1563G>A		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44144 AN: 151906 Hom.: 6655 Cov.: 31

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.277 AC: 274616 AN: 991244 Hom.: 39400 Cov.: 12 AF XY: 0.273 AC XY: 134954 AN XY: 493474

Gnomad4 AFR exome AF: 0.355

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.450

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.277

Gnomad4 NFE exome AF: 0.277

Gnomad4 OTH exome AF: 0.276

GnomAD4 genome AF: 0.291 AC: 44170 AN: 152024 Hom.: 6659 Cov.: 31 AF XY: 0.287 AC XY: 21354 AN XY: 74320

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.283

Alfa AF: 0.269 Hom.: 1173

Bravo AF: 0.293

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	9.4
Dann	Benign	0.54

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: rs2271362; hg19: chr10-120928938; COSMIC: COSV53719761; COSMIC: COSV53719761;