Variant rs2277413 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002864.3(PZP):c.2438T>C(p.Val813Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,602,598 control chromosomes in the GnomAD database, including 80,844 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.32 ( 7912 hom., cov: 32)

Exomes 𝑓: 0.31 ( 72932 hom. )

Consequence

PZP
NM_002864.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.13

Variant links:

Genes affected

PZP (HGNC:9750): (PZP alpha-2-macroglobulin like) The protein encoded by this gene is highly expressed in late-pregnancy serum and is similar in structure to alpha-2-macroglobulin. The encoded protein, which acts as a homotetramer, inhibits the activity of all four classes of proteinases. This protein contains cleavage sites for several proteinases. Upon binding of a proteinase, the conformation of this protein changes to trap the proteinase, limiting its activity. This protein appears to be elevated in the sera of presymptomatic Alzheimer's disease patients. [provided by RefSeq, Dec 2016]

PZP links:

KLRG1 (HGNC:):

KLRG1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.5282475E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PZP	NM_002864.3 linkuse as main transcript	c.2438T>C	p.Val813Ala	missense_variant	19/36	ENST00000261336.7	NP_002855.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PZP	ENST00000261336.7 linkuse as main transcript	c.2438T>C	p.Val813Ala	missense_variant	19/36	1	NM_002864.3	ENSP00000261336	P1	P20742-1

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48228

AN:

151934

Hom.:

7917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.544

Gnomad SAS

AF:

0.461

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.320

GnomAD3 exomes

AF:

0.323

AC:

80681

AN:

250108

Hom.:

14357

AF XY:

0.333

AC XY:

45017

AN XY:

135114

show subpopulations

Gnomad AFR exome

AF:

0.332

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.326

Gnomad EAS exome

AF:

0.555

Gnomad SAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.298

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.307

AC:

445945

AN:

1450546

Hom.:

72932

Cov.:

AF XY:

0.313

AC XY:

225864

AN XY:

720878

show subpopulations

Gnomad4 AFR exome

AF:

0.332

Gnomad4 AMR exome

AF:

0.197

Gnomad4 ASJ exome

AF:

0.329

Gnomad4 EAS exome

AF:

0.511

Gnomad4 SAS exome

AF:

0.464

Gnomad4 FIN exome

AF:

0.253

Gnomad4 NFE exome

AF:

0.292

Gnomad4 OTH exome

AF:

0.325

GnomAD4 genome

AF:

0.317

AC:

48238

AN:

152052

Hom.:

7912

Cov.:

AF XY:

0.320

AC XY:

23782

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.336

Gnomad4 AMR

AF:

0.265

Gnomad4 ASJ

AF:

0.323

Gnomad4 EAS

AF:

0.544

Gnomad4 SAS

AF:

0.460

Gnomad4 FIN

AF:

0.257

Gnomad4 NFE

AF:

0.298

Gnomad4 OTH

AF:

0.320

Alfa

AF:

0.304

Hom.:

3088

Bravo

AF:

0.316

ESP6500AA

AF:

0.332

AC:

1464

ESP6500EA

AF:

0.295

AC:

2537

ExAC

AF:

0.330

AC:

40022

Asia WGS

AF:

0.463

AC:

1609

AN:

3478

EpiCase

AF:

0.319

EpiControl

AF:

0.315

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.4

DANN

Benign

0.25

DEOGEN2

Benign

0.011

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.11

MetaRNN

Benign

0.0000065

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.1

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

2.1

REVEL

Benign

0.025

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.016

MPC

0.10

ClinPred

0.00030

GERP RS

-0.93

Varity_R

0.030

gMVP

0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over