Variant chr1-173487796-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004905.3(PRDX6):c.608C>T(p.Pro203Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

PRDX6
NM_004905.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.43

Variant links:

Genes affected

PRDX6 (HGNC:16753): (peroxiredoxin 6) The protein encoded by this gene is a member of the thiol-specific antioxidant protein family. This protein is a bifunctional enzyme with two distinct active sites. It is involved in redox regulation of the cell; it can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides. It may play a role in the regulation of phospholipid turnover as well as in protection against oxidative injury. [provided by RefSeq, Jul 2008]

PRDX6 links:

PRDX6-AS1 (HGNC:54870): (PRDX6 antisense RNA 1)

PRDX6-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35681415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDX6	NM_004905.3 link	c.608C>T	p.Pro203Leu	missense_variant	5/5	ENST00000340385.6	NP_004896.1	P30041V9HWC7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRDX6	ENST00000340385.6 link	c.608C>T	p.Pro203Leu	missense_variant	5/5	1	NM_004905.3	ENSP00000342026.5	P30041
PRDX6	ENST00000470017.1 link	n.640C>T		non_coding_transcript_exon_variant	4/4	2
PRDX6-AS1	ENST00000669220.1 link	n.117+1495G>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000103

AC:

AN:

251386

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000383

AC:

AN:

1461778

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000276

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000101

Hom.:

Bravo

AF:

0.000344

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000132

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

May 14, 2024

The c.608C>T (p.P203L) alteration is located in exon 5 (coding exon 5) of the PRDX6 gene. This alteration results from a C to T substitution at nucleotide position 608, causing the proline (P) at amino acid position 203 to be replaced by a leucine (L). 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

0.47

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.69

MutationAssessor

Pathogenic

4.4

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-8.2

REVEL

Uncertain

0.39

Sift

Uncertain

0.012

Sift4G

Uncertain

0.011

Polyphen

0.70

Vest4

0.62

MVP

0.69

MPC

0.65

ClinPred

0.98

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.69

gMVP

0.68

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