X-23671600-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006406.2(PRDX4):c.313G>A(p.Asp105Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,205,613 control chromosomes in the GnomAD database, including 20 homozygotes. There are 456 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (11 hom., 212 hem., cov: 23)
  • Exomes 𝑓: 0.00083 (9 hom. 244 hem.)
• Consequence: PRDX4 NM_006406.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 9.60

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009811461).
• BP6: Variant X-23671600-G-A is Benign according to our data. Variant chrX-23671600-G-A is described in ClinVar as [Benign]. Clinvar id is 784430.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00722 (811/112354) while in subpopulation AFR AF= 0.0249 (773/30997). AF 95% confidence interval is 0.0235. There are 11 homozygotes in gnomad4. There are 212 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDX4	NM_006406.2	c.313G>A	p.Asp105Asn	missense_variant	2/7	ENST00000379341.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDX4	ENST00000379341.9	c.313G>A	p.Asp105Asn	missense_variant	2/7	1	NM_006406.2	P1
PRDX4	ENST00000379331.3	c.313G>A	p.Asp105Asn	missense_variant	2/3	2
PRDX4	ENST00000379349.5	c.271G>A	p.Asp91Asn	missense_variant	2/4	3
PRDX4	ENST00000495599.1	n.425G>A		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes AF: 0.00722 AC: 811 AN: 112301 Hom.: 11 Cov.: 23 AF XY: 0.00616 AC XY: 212 AN XY: 34429

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00227

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.000113

Gnomad OTH AF: 0.00463

GnomAD3 exomes AF: 0.00196 AC: 345 AN: 175936 Hom.: 5 AF XY: 0.000903 AC XY: 55 AN XY: 60938

Gnomad AFR exome AF: 0.0237

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000752

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000831 AC: 908 AN: 1093259 Hom.: 9 Cov.: 29 AF XY: 0.000679 AC XY: 244 AN XY: 359091

Gnomad4 AFR exome AF: 0.0252

Gnomad4 AMR exome AF: 0.00166

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000565

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000111

Gnomad4 OTH exome AF: 0.00194

GnomAD4 genome AF: 0.00722 AC: 811 AN: 112354 Hom.: 11 Cov.: 23 AF XY: 0.00615 AC XY: 212 AN XY: 34492

Gnomad4 AFR AF: 0.0249

Gnomad4 AMR AF: 0.00227

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000113

Gnomad4 OTH AF: 0.00458

Alfa AF: 0.000768 Hom.: 31

Bravo AF: 0.00851

ESP6500AA AF: 0.0198 AC: 76

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.00239 AC: 290

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 25, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
Cadd	Pathogenic	26
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.059	T;T;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D
MetaRNN	Benign	0.0098	T;T;T
MetaSVM	Benign	-0.73	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-4.1	D;D;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0080	D;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		0.71	.;P;.
Vest4		0.75, 0.75
MVP		0.81
MPC		1.7
ClinPred		0.073	T
GERP RS		5.3
Varity_R		0.83
gMVP		0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs144393327; hg19: chrX-23689717; COSMIC: COSV99062117; COSMIC: COSV99062117;