10-119169426-C-T

Variant names:

• chr10-119169426-C-T
• rs2271362
• NM_006793.5:c.552-84G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006793.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDX3	NM_006793.5	MANE Select	c.552-84G>A		intron	N/A	NP_006784.1	P30048-1
	PRDX3	NM_001302272.2		c.552-893G>A		intron	N/A	NP_001289201.1
	PRDX3	NR_126102.2		n.441-84G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDX3	ENST00000298510.4	TSL:1 MANE Select	c.552-84G>A		intron	N/A	ENSP00000298510.2	P30048-1
	PRDX3	ENST00000494433.1	TSL:1	n.1563G>A		non_coding_transcript_exon	Exon 1 of 2
	PRDX3	ENST00000865262.1		c.699-84G>A		intron	N/A	ENSP00000535321.1

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

African (AFR) AF: 0.355 AC: 7812 AN: 22002

American (AMR) AF: 0.157 AC: 3265 AN: 20748

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 5234 AN: 18348

East Asian (EAS) AF: 0.450 AC: 14580 AN: 32432

South Asian (SAS) AF: 0.190 AC: 10814 AN: 56902

European-Finnish (FIN) AF: 0.277 AC: 11463 AN: 41342

Middle Eastern (MID) AF: 0.242 AC: 1025 AN: 4230

European-Non Finnish (NFE) AF: 0.277 AC: 208540 AN: 752180

Other (OTH) AF: 0.276 AC: 11883 AN: 43060

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

African (AFR) AF: 0.343 AC: 14230 AN: 41428

American (AMR) AF: 0.199 AC: 3037 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3468

East Asian (EAS) AF: 0.473 AC: 2443 AN: 5164

South Asian (SAS) AF: 0.205 AC: 990 AN: 4824

European-Finnish (FIN) AF: 0.282 AC: 2975 AN: 10564

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18415 AN: 67982

Other (OTH) AF: 0.283 AC: 596 AN: 2108

Alfa AF: 0.287 Hom.: 2957

Bravo AF: 0.293

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.4
DANN	Benign	0.54
PhyloP100		-0.032
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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