X-23682520-G-C

Variant names:

• chrX-23682520-G-C
• rs776672999
• NM_006406.2:c.724G>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_006406.2(PRDX4):​c.724G>C​(p.Gly242Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000383 in 1,045,570 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000038 (0 hom. 1 hem.)
• Consequence: PRDX4 NM_006406.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.975

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDX4	NM_006406.2	c.724G>C	p.Gly242Arg	missense_variant	Exon 5 of 7	ENST00000379341.9	NP_006397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDX4	ENST00000379341.9	c.724G>C	p.Gly242Arg	missense_variant	Exon 5 of 7	1	NM_006406.2	ENSP00000368646.4
PRDX4	ENST00000439422.1	c.355G>C	p.Gly119Arg	missense_variant	Exon 3 of 6	3		ENSP00000413736.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 0.00000383 AC: 4 AN: 1045570 Hom.: 0 Cov.: 25 AF XY: 0.00000308 AC XY: 1 AN XY: 324256

Gnomad4 AFR exome AF: 0.00

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: 0.00000493

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.48	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.54	D
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-7.8	D
REVEL	Uncertain	0.61
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.87		Loss of catalytic residue at G242 (P = 0.0892);
MVP		0.84
MPC		2.0
ClinPred		1.0	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.97
gMVP		0.90

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

Other links and lift over

dbSNP: rs776672999; hg19: chrX-23700637;