rs777372127

Variant names:

• chr1-45514916-G-A
• rs777372127
• NM_181697.3:c.340C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-45514916-G-A
• chr1-45514916-G-C

Variant summary

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

The NM_181697.3(PRDX1):​c.340C>T​(p.Gln114*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000105 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: PRDX1 NM_181697.3 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.51
• Publications: 0 publications found

Genes affected

PRDX1 (HGNC:9352): (peroxiredoxin 1) This gene encodes a member of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides. The encoded protein may play an antioxidant protective role in cells, and may contribute to the antiviral activity of CD8(+) T-cells. This protein may have a proliferative effect and play a role in cancer development or progression. Four transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jan 2011]

PRDX1 Gene-Disease associations (from GenCC):

• methylmalonic aciduria and homocystinuria type cblC

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
PRDX1	NM_181697.3	c.340C>T	p.Gln114*	stop_gained	Exon 4 of 6	ENST00000319248.13	NP_859048.1
PRDX1	NM_001202431.2	c.340C>T	p.Gln114*	stop_gained	Exon 4 of 6		NP_001189360.1
PRDX1	NM_002574.4	c.340C>T	p.Gln114*	stop_gained	Exon 4 of 6		NP_002565.1
PRDX1	NM_181696.3	c.340C>T	p.Gln114*	stop_gained	Exon 4 of 6		NP_859047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDX1	ENST00000319248.13	c.340C>T	p.Gln114*	stop_gained	Exon 4 of 6	1	NM_181697.3	ENSP00000361152.5

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251460 AF XY: 0.0000147

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727228

African (AFR) AF: 0.000209 AC: 7 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111996

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74338

African (AFR) AF: 0.000169 AC: 7 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000247 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jul 14, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with PRDX1-related conditions. This variant is present in population databases (rs777372127, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Gln114*) in the PRDX1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in PRDX1 cause disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.56
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Uncertain	0.91	D
PhyloP100		4.5
Vest4		0.82
GERP RS		6.0
BranchPoint Hunter		1.0
Mutation Taster		=2/198	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs777372127; hg19: chr1-45980588;