chr10-119177189-G-A

Variant names:

• chr10-119177189-G-A
• rs3740562
• NM_006793.5:c.37-36C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006793.5(PRDX3):​c.37-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,605,868 control chromosomes in the GnomAD database, including 90,112 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 0.37 (10800 hom., cov: 32)
  • Exomes 𝑓: 0.32 (79312 hom.)
• Consequence: PRDX3 NM_006793.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.562
• Publications: 24 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDX3	NM_006793.5	c.37-36C>T		intron_variant	Intron 1 of 6	ENST00000298510.4	NP_006784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDX3	ENST00000298510.4	c.37-36C>T		intron_variant	Intron 1 of 6	1	NM_006793.5	ENSP00000298510.2

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55605 AN: 151972 Hom.: 10785 Cov.: 32

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.349

GnomAD2 exomes AF: 0.324 AC: 78993 AN: 244052 AF XY: 0.319

Gnomad AFR exome AF: 0.483

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.356

Gnomad EAS exome AF: 0.565

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.317

Gnomad OTH exome AF: 0.327

GnomAD4 exome AF: 0.325 AC: 472398 AN: 1453778 Hom.: 79312 Cov.: 32 AF XY: 0.322 AC XY: 232992 AN XY: 723408

African (AFR) AF: 0.486 AC: 16161 AN: 33264

American (AMR) AF: 0.219 AC: 9756 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 9195 AN: 26070

East Asian (EAS) AF: 0.541 AC: 21441 AN: 39600

South Asian (SAS) AF: 0.251 AC: 21526 AN: 85910

European-Finnish (FIN) AF: 0.310 AC: 16224 AN: 52348

Middle Eastern (MID) AF: 0.291 AC: 1217 AN: 4180

European-Non Finnish (NFE) AF: 0.322 AC: 356922 AN: 1107852

Other (OTH) AF: 0.332 AC: 19956 AN: 60028

GnomAD4 genome AF: 0.366 AC: 55658 AN: 152090 Hom.: 10800 Cov.: 32 AF XY: 0.363 AC XY: 26974 AN XY: 74352

African (AFR) AF: 0.481 AC: 19945 AN: 41458

American (AMR) AF: 0.277 AC: 4232 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1302 AN: 3470

East Asian (EAS) AF: 0.544 AC: 2809 AN: 5162

South Asian (SAS) AF: 0.268 AC: 1292 AN: 4822

European-Finnish (FIN) AF: 0.313 AC: 3307 AN: 10578

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21569 AN: 67992

Other (OTH) AF: 0.350 AC: 740 AN: 2112

Alfa AF: 0.329 Hom.: 11617

Bravo AF: 0.374

Asia WGS AF: 0.374 AC: 1300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.35
DANN	Benign	0.54
PhyloP100		-0.56
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: rs3740562; hg19: chr10-120936701;