NM_006793.5:c.*448A>C

Variant names:

• chr10-119168032-T-G
• rs3377
• NM_006793.5:c.*448A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRDX3	NM_006793.5	c.*448A>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000298510.4	NP_006784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDX3	ENST00000298510.4	c.*448A>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_006793.5	ENSP00000298510.2
PRDX3	ENST00000494433.1	n.*37A>C		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

African (AFR) AF: 0.133 AC: 8 AN: 60

American (AMR) AF: 0.437 AC: 69 AN: 158

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 53 AN: 128

East Asian (EAS) AF: 0.260 AC: 25 AN: 96

South Asian (SAS) AF: 0.484 AC: 431 AN: 890

European-Finnish (FIN) AF: 0.582 AC: 292 AN: 502

Middle Eastern (MID) AF: 0.647 AC: 22 AN: 34

European-Non Finnish (NFE) AF: 0.506 AC: 2686 AN: 5306

Other (OTH) AF: 0.498 AC: 267 AN: 536

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

African (AFR) AF: 0.182 AC: 7553 AN: 41534

American (AMR) AF: 0.500 AC: 7638 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1645 AN: 3472

East Asian (EAS) AF: 0.333 AC: 1723 AN: 5176

South Asian (SAS) AF: 0.546 AC: 2635 AN: 4826

European-Finnish (FIN) AF: 0.591 AC: 6238 AN: 10552

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37194 AN: 67992

Other (OTH) AF: 0.464 AC: 978 AN: 2108

Alfa AF: 0.500 Hom.: 72862

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
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3377; hg19: chr10-120927544;