dbSNP rs776672999: PRDX4:p.Gly242Arg (chrX-23682520-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PP3_StrongBS2

The NM_006406.2(PRDX4):c.724G>A(p.Gly242Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000866 in 1,155,235 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000091 ( 0 hom., 0 hem., cov: 20)

Exomes 𝑓: 0.0000086 ( 0 hom. 3 hem. )

Consequence

PRDX4
NM_006406.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

Publications

0 publications found

Variant links:

Genes affected

PRDX4 (HGNC:17169): (peroxiredoxin 4) The protein encoded by this gene is an antioxidant enzyme and belongs to the peroxiredoxin family. The protein is localized to the cytoplasm. Peroxidases of the peroxiredoxin family reduce hydrogen peroxide and alkyl hydroperoxides to water and alcohol with the use of reducing equivalents derived from thiol-containing donor molecules. This protein has been found to play a regulatory role in the activation of the transcription factor NF-kappaB. [provided by RefSeq, Jul 2008]

PRDX4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.974

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006406.2. 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
	PRDX4	NM_006406.2	MANE Select	c.724G>A	p.Gly242Arg	missense	Exon 5 of 7	NP_006397.1	Q13162

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRDX4	ENST00000379341.9	TSL:1 MANE Select	c.724G>A	p.Gly242Arg	missense	Exon 5 of 7	ENSP00000368646.4	Q13162
PRDX4	ENST00000931168.1		c.838G>A	p.Gly280Arg	missense	Exon 6 of 8	ENSP00000601227.1
PRDX4	ENST00000887283.1		c.682G>A	p.Gly228Arg	missense	Exon 5 of 7	ENSP00000557342.1

Frequencies

GnomAD3 genomes

AF:

0.00000912

AC:

AN:

109669

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000621

AC:

AN:

160914

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000134

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000861

AC:

AN:

1045566

Hom.:

Cov.:

AF XY:

0.00000925

AC XY:

AN XY:

324252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24787

American (AMR)

AF:

0.00

AC:

AN:

31188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17809

East Asian (EAS)

AF:

0.0000371

AC:

AN:

26978

South Asian (SAS)

AF:

0.0000209

AC:

AN:

47822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37833

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3902

European-Non Finnish (NFE)

AF:

0.00000862

AC:

AN:

811876

Other (OTH)

AF:

0.00

AC:

AN:

43371

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00000912

AC:

AN:

109669

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

31929

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30080

American (AMR)

AF:

0.00

AC:

AN:

10028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2633

East Asian (EAS)

AF:

0.00

AC:

AN:

3515

South Asian (SAS)

AF:

0.00

AC:

AN:

2548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5682

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

52809

Other (OTH)

AF:

0.00

AC:

AN:

1466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Neurodevelopmental delay (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.88

MetaRNN

Pathogenic

0.97

MetaSVM

Uncertain

0.54

MutationAssessor

Pathogenic

3.3

PhyloP100

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-7.8

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.019

Polyphen

1.0

Vest4

0.78

MutPred

0.87

Loss of catalytic residue at G242 (P = 0.0892)

MVP

0.84

MPC

2.0

ClinPred

0.99

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.97

gMVP

0.90

Mutation Taster

=11/89

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over