Genetic Variant PRXL2B:p.Pro73His (chr1-2587245-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152371.5(PRXL2B):c.218C>A(p.Pro73His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,425,926 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P73S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PRXL2B
NM_152371.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.803

Publications

0 publications found

Variant links:

Genes affected

PRXL2B (HGNC:28390): (peroxiredoxin like 2B) Predicted to enable antioxidant activity and prostaglandin-F synthase activity. Predicted to be involved in prostaglandin biosynthetic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

PRXL2B links:

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ACMG classification

Classification was made for transcript

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=0.2665103).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152371.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PRXL2B	NM_152371.5	MANE Select	c.218C>A	p.Pro73His	missense	Exon 2 of 7	NP_689584.5
PRXL2B	NM_001195736.3		c.218C>A	p.Pro73His	missense	Exon 2 of 7	NP_001182665.4
PRXL2B	NM_001195737.3		c.218C>A	p.Pro73His	missense	Exon 2 of 7	NP_001182666.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRXL2B	ENST00000419916.8	TSL:1 MANE Select	c.218C>A	p.Pro73His	missense	Exon 2 of 7	ENSP00000394405.4	Q8TBF2-1
PRXL2B	ENST00000444521.6	TSL:2	c.308C>A	p.Pro103His	missense	Exon 2 of 7	ENSP00000413218.3	A0A0A0MT35
PRXL2B	ENST00000378424.9	TSL:5	c.218C>A	p.Pro73His	missense	Exon 2 of 7	ENSP00000367681.5	Q8TBF2-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000527

AC:

AN:

189744

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000121

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1425926

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707834

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32900

American (AMR)

AF:

0.00

AC:

AN:

41562

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25634

East Asian (EAS)

AF:

0.00

AC:

AN:

38084

South Asian (SAS)

AF:

0.00

AC:

AN:

82560

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39832

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1100316

Other (OTH)

AF:

0.00

AC:

AN:

59302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

Eigen

Benign

0.043

Eigen_PC

Benign

-0.058

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.84

M_CAP

Benign

0.047

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.87

PhyloP100

0.80

PrimateAI

Uncertain

0.76

REVEL

Benign

0.21

Sift4G

Uncertain

0.016

Polyphen

0.88

Vest4

0.43

MutPred

0.38

Gain of sheet (P = 0.0477)

MVP

0.53

MPC

0.65

ClinPred

0.60

GERP RS

3.9

PromoterAI

-0.13

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.53

gMVP

0.70

Mutation Taster

=84/16

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over