Variant 12-9157290-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002864.3(PZP):c.3435C>T(p.Thr1145Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00416 in 1,614,060 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 24 hom. )

Consequence

PZP
NM_002864.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0730

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:6380): (killer cell lectin like receptor G1) Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. The protein encoded by this gene belongs to the killer cell lectin-like receptor (KLR) family, which is a group of transmembrane proteins preferentially expressed in NK cells. Studies in mice suggested that the expression of this gene may be regulated by MHC class I molecules. [provided by RefSeq, Jun 2016]

KLRG1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 12-9157290-G-A is Benign according to our data. Variant chr12-9157290-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642692.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.073 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PZP	NM_002864.3 linkuse as main transcript	c.3435C>T	p.Thr1145Thr	synonymous_variant	28/36	ENST00000261336.7	NP_002855.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PZP	ENST00000261336.7 linkuse as main transcript	c.3435C>T	p.Thr1145Thr	synonymous_variant	28/36	1	NM_002864.3	ENSP00000261336.2	P20742-1
PZP	ENST00000535230.5 linkuse as main transcript	n.*2904C>T		non_coding_transcript_exon_variant	25/33	1		ENSP00000440811.1	F5GXY0
PZP	ENST00000535230.5 linkuse as main transcript	n.*2904C>T		3_prime_UTR_variant	25/33	1		ENSP00000440811.1	F5GXY0

Frequencies

GnomAD3 genomes

AF:

0.00274

AC:

417

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00511

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00439

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00257

AC:

645

AN:

250744

Hom.:

AF XY:

0.00268

AC XY:

363

AN XY:

135508

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00157

Gnomad FIN exome

AF:

0.000509

Gnomad NFE exome

AF:

0.00409

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.00431

AC:

6306

AN:

1461766

Hom.:

Cov.:

AF XY:

0.00421

AC XY:

3058

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.00280

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00144

Gnomad4 FIN exome

AF:

0.000524

Gnomad4 NFE exome

AF:

0.00516

Gnomad4 OTH exome

AF:

0.00422

GnomAD4 genome

AF:

0.00273

AC:

416

AN:

152294

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

170

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00440

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00349

Hom.:

Bravo

AF:

0.00329

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00436

EpiControl

AF:

0.00326

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

PZP: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

DANN

Benign

0.49

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over