dbSNP rs3024719: PROZ:c.71-103G>A (chr13-113159911-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003891.3(PROZ):c.71-103G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,408,294 control chromosomes in the GnomAD database, including 26,468 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 0.15 ( 2217 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24251 hom. )

Consequence

PROZ
NM_003891.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.480

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

protein Z deficiency
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

PROZ links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROZ	NM_003891.3 link	c.71-103G>A		intron_variant	Intron 1 of 7	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.71-103G>A		intron_variant	Intron 1 of 7	1	NM_003891.3	ENSP00000364697.2		P22891-1
PROZ	ENST00000342783.5 link	c.137-103G>A		intron_variant	Intron 2 of 8	1		ENSP00000344458.4		P22891-2

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22131

AN:

152142

Hom.:

2225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0315

Gnomad AMI

AF:

0.0637

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.147

GnomAD4 exome

AF:

0.182

AC:

229198

AN:

1256034

Hom.:

24251

AF XY:

0.190

AC XY:

120343

AN XY:

635044

show subpopulations

African (AFR)

AF:

0.0285

AC:

836

AN:

29294

American (AMR)

AF:

0.246

AC:

10922

AN:

44330

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

2840

AN:

24836

East Asian (EAS)

AF:

0.312

AC:

12079

AN:

38690

South Asian (SAS)

AF:

0.385

AC:

31438

AN:

81634

European-Finnish (FIN)

AF:

0.205

AC:

10544

AN:

51416

Middle Eastern (MID)

AF:

0.145

AC:

553

AN:

3808

European-Non Finnish (NFE)

AF:

0.162

AC:

150573

AN:

928470

Other (OTH)

AF:

0.176

AC:

9413

AN:

53556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

9859

19719

29578

39438

49297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5102

10204

15306

20408

25510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.145

AC:

22129

AN:

152260

Hom.:

2217

Cov.:

AF XY:

0.153

AC XY:

11383

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0315

AC:

1311

AN:

41584

American (AMR)

AF:

0.172

AC:

2624

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

406

AN:

3468

East Asian (EAS)

AF:

0.336

AC:

1738

AN:

5174

South Asian (SAS)

AF:

0.395

AC:

1903

AN:

4816

European-Finnish (FIN)

AF:

0.222

AC:

2358

AN:

10604

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.167

AC:

11385

AN:

68002

Other (OTH)

AF:

0.147

AC:

311

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

949

1899

2848

3798

4747

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0945

Hom.:

164

Bravo

AF:

0.132

Asia WGS

AF:

0.396

AC:

1372

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.085

(source)

DANN

Benign

0.67

PhyloP100

-0.48

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over