X-23682515-A-G

Variant names:

• chrX-23682515-A-G
• rs983990703
• NM_006406.2:c.719A>G

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.719A>G​(p.Lys240Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000571 in 1,050,579 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000057 (0 hom. 4 hem.)
• Consequence: PRDX4 NM_006406.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1962902).
• BS2: High Hemizygotes in GnomAdExome4 at 4 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.719A>G	p.Lys240Arg	missense	Exon 5 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.719A>G	p.Lys240Arg	missense	Exon 5 of 7	ENSP00000368646.4	Q13162
	PRDX4	ENST00000931168.1		c.833A>G	p.Lys278Arg	missense	Exon 6 of 8	ENSP00000601227.1
	PRDX4	ENST00000887283.1		c.677A>G	p.Lys226Arg	missense	Exon 5 of 7	ENSP00000557342.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD2 exomes AF: 0.00000612 AC: 1 AN: 163287 AF XY: 0.0000189

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: 0.0000133

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000571 AC: 6 AN: 1050579 Hom.: 0 Cov.: 26 AF XY: 0.0000122 AC XY: 4 AN XY: 327213

African (AFR) AF: 0.00 AC: 0 AN: 25001

American (AMR) AF: 0.00 AC: 0 AN: 31573

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17971

East Asian (EAS) AF: 0.00 AC: 0 AN: 27282

South Asian (SAS) AF: 0.00 AC: 0 AN: 48452

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38095

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3921

European-Non Finnish (NFE) AF: 0.00000614 AC: 5 AN: 814674

Other (OTH) AF: 0.0000229 AC: 1 AN: 43610

GnomAD4 genome Cov.: 20

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	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		5.0
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.17
Sift	Benign	0.030	D
Sift4G	Uncertain	0.013	D
Polyphen		0.0	B
Vest4		0.26
MutPred		0.47		Loss of methylation at K240 (P = 0.027)
MVP		0.57
MPC		0.61
ClinPred		0.58	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.64
gMVP		0.54
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: rs983990703; hg19: chrX-23700632;