Variant chrX-23667754-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006406.2(PRDX4):c.184G>A(p.Gly62Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,098,055 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

PRDX4
NM_006406.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.26

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:

PRDX4 (HGNC:):

PRDX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDX4	NM_006406.2 linkuse as main transcript	c.184G>A	p.Gly62Arg	missense_variant	1/7	ENST00000379341.9	NP_006397.1	Q13162V9HW63

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRDX4	ENST00000379341.9 linkuse as main transcript	c.184G>A	p.Gly62Arg	missense_variant	1/7	1	NM_006406.2	ENSP00000368646.4	Q13162
PRDX4	ENST00000379331.3 linkuse as main transcript	c.184G>A	p.Gly62Arg	missense_variant	1/3	2		ENSP00000368635.3	A6NG45
PRDX4	ENST00000379349.5 linkuse as main transcript	c.199+3036G>A		intron_variant		3		ENSP00000368654.1	A6NJJ0
PRDX4	ENST00000495599.1 linkuse as main transcript	n.256G>A		non_coding_transcript_exon_variant	1/5	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

111902

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34080

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000933

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000552

AC:

AN:

181035

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66889

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098055

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363487

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000894

AC:

AN:

111902

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34080

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000933

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.184G>A (p.G62R) alteration is located in exon 1 (coding exon 1) of the PRDX4 gene. This alteration results from a G to A substitution at nucleotide position 184, causing the glycine (G) at amino acid position 62 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.16

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Pathogenic

0.48

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.24

Sift

Uncertain

0.023

D;T

Sift4G

Benign

0.11

T;T

Polyphen

0.016

B;.

Vest4

0.64

MutPred

0.17

Gain of catalytic residue at G62 (P = 0.0623);Gain of catalytic residue at G62 (P = 0.0623);

MVP

0.79

MPC

0.89

ClinPred

0.50

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.53

gMVP

0.88

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over