Genetic Variant NM_006793.5:c.692C>G (chr10-119169202-G-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006793.5(PRDX3):c.692C>G(p.Ala231Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A231V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PRDX3
NM_006793.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.07

Publications

0 publications found

Variant links:

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

PRDX3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.935

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRDX3	NM_006793.5	MANE Select	c.692C>G	p.Ala231Gly	missense	Exon 6 of 7	NP_006784.1	P30048-1
PRDX3	NM_001302272.2		c.552-669C>G		intron	N/A	NP_001289201.1
PRDX3	NR_126102.2		n.581C>G		non_coding_transcript_exon	Exon 5 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRDX3	ENST00000298510.4	TSL:1 MANE Select	c.692C>G	p.Ala231Gly	missense	Exon 6 of 7	ENSP00000298510.2	P30048-1
PRDX3	ENST00000494433.1	TSL:1	n.1787C>G		non_coding_transcript_exon	Exon 1 of 2
PRDX3	ENST00000865262.1		c.839C>G	p.Ala280Gly	missense	Exon 6 of 7	ENSP00000535321.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.061

MetaRNN

Pathogenic

0.93

MetaSVM

Uncertain

0.62

MutationAssessor

Pathogenic

4.6

PhyloP100

8.1

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.97

Vest4

0.77

MutPred

0.82

Loss of glycosylation at T234 (P = 0.1149)

MVP

0.88

MPC

0.33

ClinPred

1.0

GERP RS

5.2

Varity_R

0.91

gMVP

0.68

Mutation Taster

=24/76

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over