Variant chr13-113160968-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003891.3(PROZ):c.255T>C(p.Tyr85=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,606,574 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 22 hom., cov: 33)

Exomes 𝑓: 0.00078 ( 13 hom. )

Consequence

PROZ
NM_003891.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.610

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 13-113160968-T-C is Benign according to our data. Variant chr13-113160968-T-C is described in ClinVar as [Benign]. Clinvar id is 734833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.61 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00738 (1125/152366) while in subpopulation AFR AF= 0.0252 (1047/41580). AF 95% confidence interval is 0.0239. There are 22 homozygotes in gnomad4. There are 524 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1125 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROZ	NM_003891.3 linkuse as main transcript	c.255T>C	p.Tyr85=	synonymous_variant	3/8	ENST00000375547.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROZ	ENST00000375547.7 linkuse as main transcript	c.255T>C	p.Tyr85=	synonymous_variant	3/8	1	NM_003891.3	P2	P22891-1
PROZ	ENST00000342783.5 linkuse as main transcript	c.321T>C	p.Tyr107=	synonymous_variant	4/9	1		A2	P22891-2

Frequencies

GnomAD3 genomes

AF:

0.00738

AC:

1123

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0252

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00217

AC:

545

AN:

251456

Hom.:

AF XY:

0.00157

AC XY:

213

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0279

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000778

AC:

1132

AN:

1454208

Hom.:

Cov.:

AF XY:

0.000642

AC XY:

465

AN XY:

723970

show subpopulations

Gnomad4 AFR exome

AF:

0.0247

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000107

Gnomad4 OTH exome

AF:

0.00158

GnomAD4 genome

AF:

0.00738

AC:

1125

AN:

152366

Hom.:

Cov.:

AF XY:

0.00703

AC XY:

524

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0252

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00363

Hom.:

Bravo

AF:

0.00829

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.3

DANN

Benign

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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