rs12822596

Variant summary

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

The NM_002864.3(PZP):​c.3370-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,566,490 control chromosomes in the GnomAD database, including 70,369 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5626 hom., cov: 32)
Exomes 𝑓: 0.30 ( 64743 hom. )

Consequence

PZP
NM_002864.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.18
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PZPNM_002864.3 linkuse as main transcriptc.3370-44C>T intron_variant ENST00000261336.7 NP_002855.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PZPENST00000261336.7 linkuse as main transcriptc.3370-44C>T intron_variant 1 NM_002864.3 ENSP00000261336 P1P20742-1
PZPENST00000535230.5 linkuse as main transcriptc.*2839-44C>T intron_variant, NMD_transcript_variant 1 ENSP00000440811

Frequencies

GnomAD3 genomes
AF:
0.255
AC:
38710
AN:
152002
Hom.:
5621
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.133
Gnomad AMI
AF:
0.268
Gnomad AMR
AF:
0.327
Gnomad ASJ
AF:
0.225
Gnomad EAS
AF:
0.0633
Gnomad SAS
AF:
0.206
Gnomad FIN
AF:
0.356
Gnomad MID
AF:
0.222
Gnomad NFE
AF:
0.316
Gnomad OTH
AF:
0.249
GnomAD3 exomes
AF:
0.273
AC:
62820
AN:
230300
Hom.:
9500
AF XY:
0.270
AC XY:
33896
AN XY:
125324
show subpopulations
Gnomad AFR exome
AF:
0.139
Gnomad AMR exome
AF:
0.353
Gnomad ASJ exome
AF:
0.222
Gnomad EAS exome
AF:
0.0692
Gnomad SAS exome
AF:
0.206
Gnomad FIN exome
AF:
0.353
Gnomad NFE exome
AF:
0.311
Gnomad OTH exome
AF:
0.284
GnomAD4 exome
AF:
0.296
AC:
418624
AN:
1414370
Hom.:
64743
Cov.:
27
AF XY:
0.293
AC XY:
205169
AN XY:
700908
show subpopulations
Gnomad4 AFR exome
AF:
0.130
Gnomad4 AMR exome
AF:
0.350
Gnomad4 ASJ exome
AF:
0.215
Gnomad4 EAS exome
AF:
0.0593
Gnomad4 SAS exome
AF:
0.210
Gnomad4 FIN exome
AF:
0.347
Gnomad4 NFE exome
AF:
0.315
Gnomad4 OTH exome
AF:
0.270
GnomAD4 genome
AF:
0.255
AC:
38740
AN:
152120
Hom.:
5626
Cov.:
32
AF XY:
0.256
AC XY:
19064
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.133
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:
0.249
Alfa
AF:
0.291
Hom.:
3581
Bravo
AF:
0.245
Asia WGS
AF:
0.154
AC:
535
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
6.2
DANN
Benign
0.55

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.

Other links and lift over

dbSNP: rs12822596; hg19: chr12-9309995; COSMIC: COSV54373395; COSMIC: COSV54373395; API