10-119169426-C-A

Variant names:

• chr10-119169426-C-A
• rs2271362
• NM_006793.5:c.552-84G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006793.5(PRDX3):​c.552-84G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000101 in 993,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: PRDX3 NM_006793.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.552-84G>T		intron	N/A	NP_006784.1	P30048-1
	PRDX3	NM_001302272.2		c.552-893G>T		intron	N/A	NP_001289201.1
	PRDX3	NR_126102.2		n.441-84G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDX3	ENST00000298510.4	TSL:1 MANE Select	c.552-84G>T		intron	N/A	ENSP00000298510.2	P30048-1
	PRDX3	ENST00000494433.1	TSL:1	n.1563G>T		non_coding_transcript_exon	Exon 1 of 2
	PRDX3	ENST00000865262.1		c.699-84G>T		intron	N/A	ENSP00000535321.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000101 AC: 1 AN: 993478 Hom.: 0 Cov.: 12 AF XY: 0.00000202 AC XY: 1 AN XY: 494570

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22072

American (AMR) AF: 0.00 AC: 0 AN: 20782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18380

East Asian (EAS) AF: 0.00 AC: 0 AN: 32470

South Asian (SAS) AF: 0.00 AC: 0 AN: 57056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4248

European-Non Finnish (NFE) AF: 0.00000133 AC: 1 AN: 753900

Other (OTH) AF: 0.00 AC: 0 AN: 43140

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 2957

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.9
DANN	Benign	0.52
PhyloP100		-0.032

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

Other links and lift over

dbSNP: rs2271362; hg19: chr10-120928938;