X-23671559-C-T

Variant names:

• chrX-23671559-C-T
• NM_006406.2:c.272C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006406.2(PRDX4):​c.272C>T​(p.Thr91Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000914 in 1,093,532 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: PRDX4 NM_006406.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDX4	NM_006406.2	c.272C>T	p.Thr91Ile	missense_variant	Exon 2 of 7	ENST00000379341.9	NP_006397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDX4	ENST00000379341.9	c.272C>T	p.Thr91Ile	missense_variant	Exon 2 of 7	1	NM_006406.2	ENSP00000368646.4
PRDX4	ENST00000379331.3	c.272C>T	p.Thr91Ile	missense_variant	Exon 2 of 3	2		ENSP00000368635.3
PRDX4	ENST00000379349.5	c.230C>T	p.Thr77Ile	missense_variant	Exon 2 of 4	3		ENSP00000368654.1
PRDX4	ENST00000495599.1	n.384C>T		non_coding_transcript_exon_variant	Exon 3 of 5	3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.14e-7 AC: 1 AN: 1093532 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 359406

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.053	T;T;T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Pathogenic	0.46	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	.;L;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.2	D;D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.040	D;T;D
Polyphen		0.82	.;P;.
Vest4		0.68, 0.69
MutPred		0.36		.;Loss of phosphorylation at Y87 (P = 0.1249);Loss of phosphorylation at Y87 (P = 0.1249);
MVP		0.90
MPC		1.8
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.80
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-23689676;