Variant X-23667598-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006406.2(PRDX4):c.28A>G(p.Thr10Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,190,830 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.0000056 ( 0 hom. 1 hem. )

Consequence

PRDX4
NM_006406.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.621

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12545973).

BS2

High Hemizygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDX4	NM_006406.2 linkuse as main transcript	c.28A>G	p.Thr10Ala	missense_variant	1/7	ENST00000379341.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PRDX4	ENST00000379341.9 linkuse as main transcript	c.28A>G	p.Thr10Ala	missense_variant	1/7	1	NM_006406.2	P1
PRDX4	ENST00000379331.3 linkuse as main transcript	c.28A>G	p.Thr10Ala	missense_variant	1/3	2
PRDX4	ENST00000379349.5 linkuse as main transcript	c.199+2880A>G		intron_variant		3
PRDX4	ENST00000495599.1 linkuse as main transcript	n.100A>G		non_coding_transcript_exon_variant	1/5	3

Frequencies

GnomAD3 genomes

AF:

0.0000621

AC:

AN:

112781

Hom.:

Cov.:

AF XY:

0.0000572

AC XY:

AN XY:

34957

show subpopulations

Gnomad AFR

AF:

0.0000642

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000370

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:

0.000654

GnomAD4 exome

AF:

0.00000557

AC:

AN:

1078049

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

350823

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000125

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:

0.0000442

GnomAD4 genome

AF:

0.0000621

AC:

AN:

112781

Hom.:

Cov.:

AF XY:

0.0000572

AC XY:

AN XY:

34957

show subpopulations

Gnomad4 AFR

AF:

0.0000642

Gnomad4 AMR

AF:

0.000370

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:

0.000654

Bravo

AF:

0.000181

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

Dec 09, 2023

The c.28A>G (p.T10A) alteration is located in exon 1 (coding exon 1) of the PRDX4 gene. This alteration results from a A to G substitution at nucleotide position 28, causing the threonine (T) at amino acid position 10 to be replaced by an alanine (A). 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

Benign

0.048

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

Cadd

Benign

1.9

Dann

Benign

0.79

DEOGEN2

Benign

0.13

T;T

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.052

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.12

N;N

REVEL

Benign

0.044

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.13

T;D

Polyphen

0.0

B;.

Vest4

0.15

MutPred

0.18

Loss of glycosylation at T10 (P = 0.0258);Loss of glycosylation at T10 (P = 0.0258);

MVP

0.54

MPC

0.73

ClinPred

0.67

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.066

gMVP

0.33

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