NM_006406.2:c.802G>A

Variant names:

• chrX-23686321-G-A
• rs866087799
• NM_006406.2:c.802G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006406.2(PRDX4):​c.802G>A​(p.Asp268Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000256 in 1,170,535 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 9.4e-7 (0 hom. 1 hem.)
• Consequence: PRDX4 NM_006406.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.88
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22882149).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006406.2. 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
	PRDX4	NM_006406.2	MANE Select	c.802G>A	p.Asp268Asn	missense	Exon 7 of 7	NP_006397.1	Q13162

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDX4	ENST00000379341.9	TSL:1 MANE Select	c.802G>A	p.Asp268Asn	missense	Exon 7 of 7	ENSP00000368646.4	Q13162
	PRDX4	ENST00000931168.1		c.916G>A	p.Asp306Asn	missense	Exon 8 of 8	ENSP00000601227.1
	PRDX4	ENST00000887283.1		c.760G>A	p.Asp254Asn	missense	Exon 7 of 7	ENSP00000557342.1

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112275 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000646

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 160718 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.45e-7 AC: 1 AN: 1058260 Hom.: 0 Cov.: 25 AF XY: 0.00000298 AC XY: 1 AN XY: 335046

African (AFR) AF: 0.00 AC: 0 AN: 24978

American (AMR) AF: 0.00 AC: 0 AN: 29119

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18392

East Asian (EAS) AF: 0.0000340 AC: 1 AN: 29450

South Asian (SAS) AF: 0.00 AC: 0 AN: 48519

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3949

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 819393

Other (OTH) AF: 0.00 AC: 0 AN: 44416

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112275 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34459

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000646 AC: 2 AN: 30946

American (AMR) AF: 0.00 AC: 0 AN: 10550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3601

South Asian (SAS) AF: 0.00 AC: 0 AN: 2755

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53279

Other (OTH) AF: 0.00 AC: 0 AN: 1513

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.5	N
PhyloP100		6.9
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.12
Sift	Benign	0.22	T
Sift4G	Benign	0.37	T
Polyphen		0.0	B
Vest4		0.45
MVP		0.54
MPC		0.72
ClinPred		0.87	D
GERP RS		5.1
Varity_R		0.63
gMVP		0.60
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs866087799; hg19: chrX-23704438; COSMIC: COSV101028678;