13-113158648-G-A

Variant summary

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

The NM_003891.3(PROZ):​c.-13G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 1,596,626 control chromosomes in the GnomAD database, including 626,754 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 0.81 ( 51325 hom., cov: 31)
Exomes 𝑓: 0.89 ( 575429 hom. )

Consequence

PROZ
NM_003891.3 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.838
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PROZNM_003891.3 linkuse as main transcriptc.-13G>A 5_prime_UTR_variant 1/8 ENST00000375547.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PROZENST00000375547.7 linkuse as main transcriptc.-13G>A 5_prime_UTR_variant 1/81 NM_003891.3 P2P22891-1
PROZENST00000342783.5 linkuse as main transcriptc.-13G>A 5_prime_UTR_variant 1/91 A2P22891-2

Frequencies

GnomAD3 genomes
AF:
0.810
AC:
123042
AN:
151862
Hom.:
51322
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.666
Gnomad AMI
AF:
0.995
Gnomad AMR
AF:
0.761
Gnomad ASJ
AF:
0.902
Gnomad EAS
AF:
0.441
Gnomad SAS
AF:
0.633
Gnomad FIN
AF:
0.872
Gnomad MID
AF:
0.899
Gnomad NFE
AF:
0.932
Gnomad OTH
AF:
0.816
GnomAD3 exomes
AF:
0.797
AC:
179295
AN:
224854
Hom.:
74515
AF XY:
0.803
AC XY:
97752
AN XY:
121728
show subpopulations
Gnomad AFR exome
AF:
0.662
Gnomad AMR exome
AF:
0.668
Gnomad ASJ exome
AF:
0.909
Gnomad EAS exome
AF:
0.429
Gnomad SAS exome
AF:
0.642
Gnomad FIN exome
AF:
0.878
Gnomad NFE exome
AF:
0.933
Gnomad OTH exome
AF:
0.840
GnomAD4 exome
AF:
0.885
AC:
1278779
AN:
1444646
Hom.:
575429
Cov.:
42
AF XY:
0.880
AC XY:
631453
AN XY:
717578
show subpopulations
Gnomad4 AFR exome
AF:
0.659
Gnomad4 AMR exome
AF:
0.679
Gnomad4 ASJ exome
AF:
0.906
Gnomad4 EAS exome
AF:
0.480
Gnomad4 SAS exome
AF:
0.649
Gnomad4 FIN exome
AF:
0.885
Gnomad4 NFE exome
AF:
0.933
Gnomad4 OTH exome
AF:
0.853
GnomAD4 genome
AF:
0.810
AC:
123081
AN:
151980
Hom.:
51325
Cov.:
31
AF XY:
0.800
AC XY:
59408
AN XY:
74266
show subpopulations
Gnomad4 AFR
AF:
0.665
Gnomad4 AMR
AF:
0.761
Gnomad4 ASJ
AF:
0.902
Gnomad4 EAS
AF:
0.442
Gnomad4 SAS
AF:
0.633
Gnomad4 FIN
AF:
0.872
Gnomad4 NFE
AF:
0.932
Gnomad4 OTH
AF:
0.813
Alfa
AF:
0.903
Hom.:
57574
Bravo
AF:
0.796
Asia WGS
AF:
0.518
AC:
1809
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
1.1
DANN
Benign
0.71

Splicing

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: rs2273971; hg19: chr13-113812962; COSMIC: COSV61439244; API