Variant 13-113163011-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_003891.3(PROZ):c.262G>A(p.Gly88Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,519,694 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000077 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

PROZ
NM_003891.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.25

Variant links:

Genes affected

PROZ (HGNC:9460): (protein Z, vitamin K dependent plasma glycoprotein) This gene encodes a liver vitamin K-dependent glycoprotein that is synthesized in the liver and secreted into the plasma. The encoded protein plays a role in regulating blood coagulation by complexing with protein Z-dependent protease inhibitor to directly inhibit activated factor X at the phospholipid surface. Deficiencies in this protein are associated with an increased risk of ischemic arterial diseases and fetal loss. Mutations in this gene are the cause of protein Z deficiency. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

PROZ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROZ	NM_003891.3 link	c.262G>A	p.Gly88Ser	missense_variant, splice_region_variant	Exon 4 of 8	ENST00000375547.7	NP_003882.1	P22891-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROZ	ENST00000375547.7 link	c.262G>A	p.Gly88Ser	missense_variant, splice_region_variant	Exon 4 of 8	1	NM_003891.3	ENSP00000364697.2		P22891-1
PROZ	ENST00000342783.5 link	c.328G>A	p.Gly110Ser	missense_variant, splice_region_variant	Exon 5 of 9	1		ENSP00000344458.4		P22891-2

Frequencies

GnomAD3 genomes

AF:

0.0000769

AC:

AN:

143132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000214

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000209

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000460

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000871

AC:

AN:

160648

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

84946

show subpopulations

Gnomad AFR exome

AF:

0.000109

Gnomad AMR exome

AF:

0.000275

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000168

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000321

Gnomad OTH exome

AF:

0.000444

GnomAD4 exome

AF:

0.0000283

AC:

AN:

1376446

Hom.:

Cov.:

AF XY:

0.0000353

AC XY:

AN XY:

679190

show subpopulations

Gnomad4 AFR exome

AF:

0.0000322

Gnomad4 AMR exome

AF:

0.000253

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000235

Gnomad4 OTH exome

AF:

0.0000533

GnomAD4 genome

AF:

0.0000768

AC:

AN:

143248

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

69554

show subpopulations

Gnomad4 AFR

AF:

0.000103

Gnomad4 AMR

AF:

0.000213

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000210

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000460

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000494

Hom.:

ESP6500AA

AF:

0.000232

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000446

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.262G>A (p.G88S) alteration is located in exon 4 (coding exon 4) of the PROZ gene. This alteration results from a G to A substitution at nucleotide position 262, causing the glycine (G) at amino acid position 88 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.84

.;D

Eigen

Benign

-0.0045

Eigen_PC

Benign

-0.085

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.72

T;T

M_CAP

Pathogenic

0.34

MetaRNN

Uncertain

0.51

D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Benign

1.5

.;L

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.3

D;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.0050

D;D

Sift4G

Benign

0.065

T;T

Polyphen

0.93

P;D

Vest4

0.25

MVP

0.98

MPC

0.60

ClinPred

0.15

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.64

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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