X-23667781-G-T

Variant names:

• chrX-23667781-G-T
• rs769435624
• NM_006406.2:c.211G>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006406.2(PRDX4):​c.211G>T​(p.Asp71Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000219 in 1,098,022 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000022 (0 hom. 7 hem.)
• Consequence: PRDX4 NM_006406.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.19

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_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDX4	NM_006406.2	c.211G>T	p.Asp71Tyr	missense_variant	Exon 1 of 7	ENST00000379341.9	NP_006397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDX4	ENST00000379341.9	c.211G>T	p.Asp71Tyr	missense_variant	Exon 1 of 7	1	NM_006406.2	ENSP00000368646.4
PRDX4	ENST00000379331.3	c.211G>T	p.Asp71Tyr	missense_variant	Exon 1 of 3	2		ENSP00000368635.3
PRDX4	ENST00000379349.5	c.199+3063G>T		intron_variant	Intron 1 of 3	3		ENSP00000368654.1
PRDX4	ENST00000495599.1	n.283G>T		non_coding_transcript_exon_variant	Exon 1 of 5	3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.0000499 AC: 9 AN: 180361 Hom.: 0 AF XY: 0.0000300 AC XY: 2 AN XY: 66701

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000509

Gnomad SAS exome AF: 0.000105

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000219 AC: 24 AN: 1098022 Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 7 AN XY: 363460

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000497

Gnomad4 SAS exome AF: 0.0000554

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000356

Gnomad4 OTH exome AF: 0.0000651

GnomAD4 genome Cov.: 24

Bravo AF: 0.0000529

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 18, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.211G>T (p.D71Y) alteration is located in exon 1 (coding exon 1) of the PRDX4 gene. This alteration results from a G to T substitution at nucleotide position 211, causing the aspartic acid (D) at amino acid position 71 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.63	D;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Pathogenic	0.55	D
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.90	P;.
Vest4		0.59
MutPred		0.39		Gain of phosphorylation at D71 (P = 0.0333);Gain of phosphorylation at D71 (P = 0.0333);
MVP		0.84
MPC		1.3
ClinPred		0.42	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -13

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs769435624; hg19: chrX-23685898;