Variant rs10842971 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.4328T>A(p.Ile1443Asn) variant causes a missense change. The variant allele was found at a frequency of 0.291 in 1,609,768 control chromosomes in the GnomAD database, including 72,065 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.25 ( 5599 hom., cov: 32)

Exomes 𝑓: 0.29 ( 66466 hom. )

Consequence

PZP
NM_002864.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.96

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=0.004720241).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PZP	NM_002864.3 linkuse as main transcript	c.4328T>A	p.Ile1443Asn	missense_variant	34/36	ENST00000261336.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PZP	ENST00000261336.7 linkuse as main transcript	c.4328T>A	p.Ile1443Asn	missense_variant	34/36	1	NM_002864.3	P1	P20742-1
PZP	ENST00000535230.5 linkuse as main transcript	c.*3797T>A		3_prime_UTR_variant, NMD_transcript_variant	31/33	1

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38516

AN:

151952

Hom.:

5594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.299

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.225

Gnomad EAS

AF:

0.0633

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.356

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.247

GnomAD3 exomes

AF:

0.271

AC:

67841

AN:

250188

Hom.:

10310

AF XY:

0.269

AC XY:

36369

AN XY:

135256

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.348

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.0680

Gnomad SAS exome

AF:

0.203

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.309

Gnomad OTH exome

AF:

0.276

GnomAD4 exome

AF:

0.295

AC:

429388

AN:

1457700

Hom.:

66466

Cov.:

AF XY:

0.292

AC XY:

211509

AN XY:

725390

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.347

Gnomad4 ASJ exome

AF:

0.213

Gnomad4 EAS exome

AF:

0.0590

Gnomad4 SAS exome

AF:

0.209

Gnomad4 FIN exome

AF:

0.348

Gnomad4 NFE exome

AF:

0.314

Gnomad4 OTH exome

AF:

0.268

GnomAD4 genome

AF:

0.253

AC:

38541

AN:

152068

Hom.:

5599

Cov.:

AF XY:

0.255

AC XY:

18992

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.328

Gnomad4 ASJ

AF:

0.225

Gnomad4 EAS

AF:

0.0634

Gnomad4 SAS

AF:

0.207

Gnomad4 FIN

AF:

0.356

Gnomad4 NFE

AF:

0.316

Gnomad4 OTH

AF:

0.247

Alfa

AF:

0.292

Hom.:

5180

Bravo

AF:

0.244

TwinsUK

AF:

0.308

AC:

1141

ALSPAC

AF:

0.314

AC:

1211

ESP6500AA

AF:

0.142

AC:

625

ESP6500EA

AF:

0.298

AC:

2559

ExAC

AF:

0.268

AC:

32548

Asia WGS

AF:

0.155

AC:

538

AN:

3478

EpiCase

AF:

0.298

EpiControl

AF:

0.286

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

Cadd

Benign

Dann

Benign

0.87

DEOGEN2

Benign

0.33

Eigen

Benign

0.035

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-6.6

REVEL

Benign

0.18

Sift

Uncertain

0.0010

Sift4G

Benign

0.092

Polyphen

1.0

Vest4

0.12

MPC

0.40

ClinPred

0.070

GERP RS

4.2

Varity_R

0.77

gMVP

0.35

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