1-45514913-C-T

Variant names:

• chr1-45514913-C-T
• rs1332306016
• NM_181697.3:c.343G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181697.3(PRDX1):​c.343G>A​(p.Asp115Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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. D115H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRDX1 NM_181697.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39326352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDX1	NM_181697.3	c.343G>A	p.Asp115Asn	missense_variant	Exon 4 of 6	ENST00000319248.13	NP_859048.1
PRDX1	NM_001202431.2	c.343G>A	p.Asp115Asn	missense_variant	Exon 4 of 6		NP_001189360.1
PRDX1	NM_002574.4	c.343G>A	p.Asp115Asn	missense_variant	Exon 4 of 6		NP_002565.1
PRDX1	NM_181696.3	c.343G>A	p.Asp115Asn	missense_variant	Exon 4 of 6		NP_859047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDX1	ENST00000319248.13	c.343G>A	p.Asp115Asn	missense_variant	Exon 4 of 6	1	NM_181697.3	ENSP00000361152.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T;T;T;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;.;.;D
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;.;.
PhyloP100		4.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Benign	0.13
Sift	Benign	0.049	D;D;D;D
Sift4G	Uncertain	0.057	T;T;.;.
Polyphen		0.0010	B;B;.;.
Vest4		0.38
MutPred		0.48		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.61
MPC		0.048
ClinPred		0.97	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.66
Mutation Taster		=18/82	disease causing

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: rs1332306016; hg19: chr1-45980585;