X-23667619-C-A

Variant names:

• chrX-23667619-C-A
• rs776033071
• NM_006406.2:c.49C>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006406.2(PRDX4):​c.49C>A​(p.His17Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000485 in 1,196,587 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000052 (0 hom. 19 hem.)
• Consequence: PRDX4 NM_006406.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.252
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07329157).
• BS2: High Hemizygotes in GnomAdExome4 at 19 gene

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.49C>A	p.His17Asn	missense	Exon 1 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.49C>A	p.His17Asn	missense	Exon 1 of 7	ENSP00000368646.4	Q13162
	PRDX4	ENST00000931168.1		c.49C>A	p.His17Asn	missense	Exon 1 of 8	ENSP00000601227.1
	PRDX4	ENST00000887283.1		c.49C>A	p.His17Asn	missense	Exon 1 of 7	ENSP00000557342.1

Frequencies

GnomAD3 genomes AF: 0.0000177 AC: 2 AN: 112873 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

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: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000686 AC: 1 AN: 145771 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: 0.0000166

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000517 AC: 56 AN: 1083714 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 19 AN XY: 353886

African (AFR) AF: 0.0000383 AC: 1 AN: 26082

American (AMR) AF: 0.00 AC: 0 AN: 32938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19075

East Asian (EAS) AF: 0.00 AC: 0 AN: 29370

South Asian (SAS) AF: 0.00 AC: 0 AN: 52546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4100

European-Non Finnish (NFE) AF: 0.0000658 AC: 55 AN: 835270

Other (OTH) AF: 0.00 AC: 0 AN: 45529

GnomAD4 genome AF: 0.0000177 AC: 2 AN: 112873 Hom.: 0 Cov.: 23 AF XY: 0.0000285 AC XY: 1 AN XY: 35029

African (AFR) AF: 0.00 AC: 0 AN: 31132

American (AMR) AF: 0.00 AC: 0 AN: 10807

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3577

South Asian (SAS) AF: 0.00 AC: 0 AN: 2802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53244

Other (OTH) AF: 0.00 AC: 0 AN: 1529

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.074
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.53
DEOGEN2	Benign	0.13	T
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.25
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.046
Sift	Benign	0.50	T
Sift4G	Benign	0.37	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.089		Loss of loop (P = 0.1242)
MVP		0.41
MPC		0.81
ClinPred		0.024	T
GERP RS		-0.53
PromoterAI		-0.064	Neutral
Varity_R		0.039
gMVP		0.20
Mutation Taster		=95/5	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: rs776033071; hg19: chrX-23685736;