NM_006793.5:c.730C>A

Variant names:

• chr10-119168521-G-T
• rs768037445
• NM_006793.5:c.730C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006793.5(PRDX3):​c.730C>A​(p.Pro244Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRDX3 NM_006793.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.25
• Publications: 0 publications found

Genes affected

PRDX3 (HGNC:9354): (peroxiredoxin 3) This gene encodes a mitochondrial protein with antioxidant function. The protein is similar to the C22 subunit of Salmonella typhimurium alkylhydroperoxide reductase, and it can rescue bacterial resistance to alkylhydroperoxide in E. coli that lack the C22 subunit. The human and mouse genes are highly conserved, and they map to the regions syntenic between mouse and human chromosomes. Sequence comparisons with recently cloned mammalian homologs suggest that these genes consist of a family that is responsible for the regulation of cellular proliferation, differentiation and antioxidant functions. This family member can protect cells from oxidative stress, and it can promote cell survival in prostate cancer. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 1, 3, 13 and 22. [provided by RefSeq, Oct 2014]

PRDX3 Gene-Disease associations (from GenCC):

• corneal dystrophy, punctiform and polychromatic pre-descemet

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• spinocerebellar ataxia, autosomal recessive 32

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20035398).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006793.5. 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
	PRDX3	NM_006793.5	MANE Select	c.730C>A	p.Pro244Thr	missense	Exon 7 of 7	NP_006784.1	P30048-1
	PRDX3	NM_001302272.2		c.564C>A	p.Val188Val	synonymous	Exon 6 of 6	NP_001289201.1
	PRDX3	NR_126102.2		n.619C>A		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDX3	ENST00000298510.4	TSL:1 MANE Select	c.730C>A	p.Pro244Thr	missense	Exon 7 of 7	ENSP00000298510.2	P30048-1
	PRDX3	ENST00000494433.1	TSL:1	n.1825C>A		non_coding_transcript_exon	Exon 2 of 2
	PRDX3	ENST00000865262.1		c.877C>A	p.Pro293Thr	missense	Exon 7 of 7	ENSP00000535321.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250600 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: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461528 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727078

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111958

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.29	T
Eigen	Benign	0.023
Eigen_PC	Benign	0.093
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		8.3
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.23
Sift	Benign	0.092	T
Sift4G	Uncertain	0.051	T
Polyphen		0.0080	B
Vest4		0.32
MutPred		0.41		Loss of ubiquitination at K248 (P = 0.0456)
MVP		0.59
MPC		0.083
ClinPred		0.72	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.76
gMVP		0.66
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs768037445; hg19: chr10-120928033;