X-23671600-G-A

Position:

chrX-23671600-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006406.2(PRDX4):c.313G>A(p.Asp105Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,205,613 control chromosomes in the GnomAD database, including 20 homozygotes. There are 456 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 11 hom., 212 hem., cov: 23)

Exomes 𝑓: 0.00083 ( 9 hom. 244 hem. )

Consequence

PRDX4
NM_006406.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 9.60

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009811461).

BP6

Variant X-23671600-G-A is Benign according to our data. Variant chrX-23671600-G-A is described in ClinVar as [Benign]. Clinvar id is 784430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00722 (811/112354) while in subpopulation AFR AF= 0.0249 (773/30997). AF 95% confidence interval is 0.0235. There are 11 homozygotes in gnomad4. There are 212 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDX4	NM_006406.2 linkuse as main transcript	c.313G>A	p.Asp105Asn	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.313G>A	p.Asp105Asn	missense_variant	2/7	1	NM_006406.2	ENSP00000368646.4	Q13162
PRDX4	ENST00000379331.3 linkuse as main transcript	c.313G>A	p.Asp105Asn	missense_variant	2/3	2		ENSP00000368635.3	A6NG45
PRDX4	ENST00000379349.5 linkuse as main transcript	c.271G>A	p.Asp91Asn	missense_variant	2/4	3		ENSP00000368654.1	A6NJJ0
PRDX4	ENST00000495599.1 linkuse as main transcript	n.425G>A		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes

AF:

0.00722

AC:

811

AN:

112301

Hom.:

Cov.:

AF XY:

0.00616

AC XY:

212

AN XY:

34429

show subpopulations

Gnomad AFR

AF:

0.0250

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00227

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.00463

GnomAD3 exomes

AF:

0.00196

AC:

345

AN:

175936

Hom.:

AF XY:

0.000903

AC XY:

AN XY:

60938

show subpopulations

Gnomad AFR exome

AF:

0.0237

Gnomad AMR exome

AF:

0.00130

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:

0.0000752

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.000831

AC:

908

AN:

1093259

Hom.:

Cov.:

AF XY:

0.000679

AC XY:

244

AN XY:

359091

show subpopulations

Gnomad4 AFR exome

AF:

0.0252

Gnomad4 AMR exome

AF:

0.00166

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000565

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000111

Gnomad4 OTH exome

AF:

0.00194

GnomAD4 genome

AF:

0.00722

AC:

811

AN:

112354

Hom.:

Cov.:

AF XY:

0.00615

AC XY:

212

AN XY:

34492

show subpopulations

Gnomad4 AFR

AF:

0.0249

Gnomad4 AMR

AF:

0.00227

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000113

Gnomad4 OTH

AF:

0.00458

Alfa

AF:

0.000768

Hom.:

Bravo

AF:

0.00851

ESP6500AA

AF:

0.0198

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00239

AC:

290

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.059

T;T;T

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D;D

MetaRNN

Benign

0.0098

T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Pathogenic

3.0

.;M;.

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-4.1

D;D;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.017

D;D;D

Polyphen

0.71

.;P;.

Vest4

0.75, 0.75

MVP

0.81

MPC

1.7

ClinPred

0.073

GERP RS

5.3

Varity_R

0.83

gMVP

0.87

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