Genetic Variant PRDX6:p.Pro2Arg (chr1-173477402-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_004905.3(PRDX6):c.5C>G(p.Pro2Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P2L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Consequence

PRDX6
NM_004905.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.79

Publications

0 publications found

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:

TNFSF4 (HGNC:11934): (TNF superfamily member 4) This gene encodes a cytokine of the tumor necrosis factor (TNF) ligand family. The encoded protein functions in T cell antigen-presenting cell (APC) interactions and mediates adhesion of activated T cells to endothelial cells. Polymorphisms in this gene have been associated with Sjogren's syndrome and systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

TNFSF4 links:

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

PRDX6-AS1 links:

LOC100506023 (HGNC:):

LOC100506023 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.781

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004905.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDX6	NM_004905.3	MANE Select	c.5C>G	p.Pro2Arg	missense	Exon 1 of 5	NP_004896.1	P30041
	LOC100506023	NR_037845.1		n.-247G>C		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRDX6	ENST00000340385.6	TSL:1 MANE Select	c.5C>G	p.Pro2Arg	missense	Exon 1 of 5	ENSP00000342026.5	P30041
PRDX6	ENST00000922555.1		c.5C>G	p.Pro2Arg	missense	Exon 1 of 6	ENSP00000592614.1
PRDX6	ENST00000867927.1		c.5C>G	p.Pro2Arg	missense	Exon 2 of 6	ENSP00000537986.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000411

AC:

AN:

243322

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000904

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.084

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.75

M_CAP

Benign

0.076

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.4

PhyloP100

6.8

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.33

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

0.89

Vest4

0.68

MutPred

0.41

Gain of methylation at P2 (P = 0.0087)

MVP

0.83

MPC

1.1

ClinPred

0.98

GERP RS

5.1

PromoterAI

-0.090

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.84

gMVP

0.59

Mutation Taster

=73/27

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over