Genetic Variant PRDX3:c.*199C>G (chr10-119168281-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006793.5(PRDX3):c.*199C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,102,234 control chromosomes in the GnomAD database, including 64,826 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 0.36 ( 10357 hom., cov: 33)

Exomes 𝑓: 0.33 ( 54469 hom. )

Consequence

PRDX3
NM_006793.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.493

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDX3	NM_006793.5 link	c.*199C>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000298510.4	NP_006784.1	P30048-1A0A384MTR2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDX3	ENST00000298510 link	c.*199C>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_006793.5	ENSP00000298510.2		P30048-1
PRDX3	ENST00000494433.1 link	n.2065C>G		non_coding_transcript_exon_variant	Exon 2 of 2	1

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54735

AN:

151896

Hom.:

10345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.451

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.341

GnomAD4 exome

AF:

0.333

AC:

316153

AN:

950220

Hom.:

54469

Cov.:

AF XY:

0.330

AC XY:

155623

AN XY:

472132

show subpopulations

Gnomad4 AFR exome

AF:

0.457

AC:

9284

AN:

20306

Gnomad4 AMR exome

AF:

0.239

AC:

3464

AN:

14508

Gnomad4 ASJ exome

AF:

0.365

AC:

6063

AN:

16616

Gnomad4 EAS exome

AF:

0.549

AC:

15715

AN:

28648

Gnomad4 SAS exome

AF:

0.253

AC:

13080

AN:

51606

Gnomad4 FIN exome

AF:

0.309

AC:

8645

AN:

28000

Gnomad4 NFE exome

AF:

0.328

AC:

245048

AN:

746240

Gnomad4 Remaining exome

AF:

0.338

AC:

13974

AN:

41382

Heterozygous variant carriers

9801

19602

29402

39203

49004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

7684

15368

23052

30736

38420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.360

AC:

54783

AN:

152014

Hom.:

10357

Cov.:

AF XY:

0.357

AC XY:

26537

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.450

AC:

0.450299

AN:

0.450299

Gnomad4 AMR

AF:

0.278

AC:

0.278273

AN:

0.278273

Gnomad4 ASJ

AF:

0.389

AC:

0.389337

AN:

0.389337

Gnomad4 EAS

AF:

0.553

AC:

0.553434

AN:

0.553434

Gnomad4 SAS

AF:

0.271

AC:

0.271197

AN:

0.271197

Gnomad4 FIN

AF:

0.315

AC:

0.314727

AN:

0.314727

Gnomad4 NFE

AF:

0.322

AC:

0.321785

AN:

0.321785

Gnomad4 OTH

AF:

0.343

AC:

0.342952

AN:

0.342952

Heterozygous variant carriers

1839

3678

5518

7357

9196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.178

Hom.:

332

Bravo

AF:

0.367

Asia WGS

AF:

0.379

AC:

1318

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.4

DANN

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over