Variant X-23671559-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006406.2(PRDX4):c.272C>G(p.Thr91Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,205,532 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 32 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000075 ( 0 hom. 30 hem. )

Consequence

PRDX4
NM_006406.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDX4	NM_006406.2 linkuse as main transcript	c.272C>G	p.Thr91Arg	missense_variant	2/7	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.272C>G	p.Thr91Arg	missense_variant	2/7	1	NM_006406.2	ENSP00000368646.4	Q13162
PRDX4	ENST00000379331.3 linkuse as main transcript	c.272C>G	p.Thr91Arg	missense_variant	2/3	2		ENSP00000368635.3	A6NG45
PRDX4	ENST00000379349.5 linkuse as main transcript	c.230C>G	p.Thr77Arg	missense_variant	2/4	3		ENSP00000368654.1	A6NJJ0
PRDX4	ENST00000495599.1 linkuse as main transcript	n.384C>G		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes

AF:

0.0000357

AC:

AN:

112001

Hom.:

Cov.:

AF XY:

0.0000585

AC XY:

AN XY:

34177

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000948

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:

0.0000563

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000284

AC:

AN:

176261

Hom.:

AF XY:

0.0000490

AC XY:

AN XY:

61211

show subpopulations

Gnomad AFR exome

AF:

0.0000781

Gnomad AMR exome

AF:

0.00

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:

0.0000500

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000750

AC:

AN:

1093531

Hom.:

Cov.:

AF XY:

0.0000835

AC XY:

AN XY:

359405

show subpopulations

Gnomad4 AFR exome

AF:

0.0000383

Gnomad4 AMR exome

AF:

0.00

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:

0.0000952

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

AF:

0.0000357

AC:

AN:

112001

Hom.:

Cov.:

AF XY:

0.0000585

AC XY:

AN XY:

34177

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000948

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000563

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

ExAC

AF:

0.0000412

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

Apr 07, 2023

The c.272C>G (p.T91R) alteration is located in exon 2 (coding exon 2) of the PRDX4 gene. This alteration results from a C to G substitution at nucleotide position 272, causing the threonine (T) at amino acid position 91 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

0.41

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

T;T;T

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

D;D;D

M_CAP

Pathogenic

0.61

MetaRNN

Uncertain

0.55

D;D;D

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.9

.;M;.

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-4.9

D;D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.029

D;D;D

Polyphen

0.99

.;D;.

Vest4

0.82, 0.87

MutPred

0.38

.;Loss of phosphorylation at Y87 (P = 0.2722);Loss of phosphorylation at Y87 (P = 0.2722);

MVP

0.90

MPC

1.9

ClinPred

0.67

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.96

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