NM_003891.3:c.-13G>A
Variant names:
Variant summary
Our verdict is Benign. The variant received -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
NM_003891.3 5_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.838
Publications
22 publications found
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 deficiencyInheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
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=-0.91).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PROZ | ENST00000375547.7 | c.-13G>A | 5_prime_UTR_variant | Exon 1 of 8 | 1 | NM_003891.3 | ENSP00000364697.2 | |||
PROZ | ENST00000342783.5 | c.-13G>A | 5_prime_UTR_variant | Exon 1 of 9 | 1 | ENSP00000344458.4 | ||||
ENSG00000304064 | ENST00000799342.1 | n.252+100C>T | intron_variant | Intron 1 of 2 |
Frequencies
GnomAD3 genomes AF: 0.810 AC: 123042AN: 151862Hom.: 51322 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
123042
AN:
151862
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.797 AC: 179295AN: 224854 AF XY: 0.803 show subpopulations
GnomAD2 exomes
AF:
AC:
179295
AN:
224854
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.885 AC: 1278779AN: 1444646Hom.: 575429 Cov.: 42 AF XY: 0.880 AC XY: 631453AN XY: 717578 show subpopulations
GnomAD4 exome
AF:
AC:
1278779
AN:
1444646
Hom.:
Cov.:
42
AF XY:
AC XY:
631453
AN XY:
717578
show subpopulations
African (AFR)
AF:
AC:
21840
AN:
33126
American (AMR)
AF:
AC:
29079
AN:
42836
Ashkenazi Jewish (ASJ)
AF:
AC:
23430
AN:
25848
East Asian (EAS)
AF:
AC:
18619
AN:
38750
South Asian (SAS)
AF:
AC:
54150
AN:
83480
European-Finnish (FIN)
AF:
AC:
44492
AN:
50272
Middle Eastern (MID)
AF:
AC:
4933
AN:
5626
European-Non Finnish (NFE)
AF:
AC:
1031251
AN:
1104946
Other (OTH)
AF:
AC:
50985
AN:
59762
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.469
Heterozygous variant carriers
0
6846
13692
20539
27385
34231
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
21268
42536
63804
85072
106340
<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: 0.810 AC: 123081AN: 151980Hom.: 51325 Cov.: 31 AF XY: 0.800 AC XY: 59408AN XY: 74266 show subpopulations
GnomAD4 genome
AF:
AC:
123081
AN:
151980
Hom.:
Cov.:
31
AF XY:
AC XY:
59408
AN XY:
74266
show subpopulations
African (AFR)
AF:
AC:
27540
AN:
41408
American (AMR)
AF:
AC:
11631
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
AC:
3128
AN:
3468
East Asian (EAS)
AF:
AC:
2259
AN:
5116
South Asian (SAS)
AF:
AC:
3042
AN:
4808
European-Finnish (FIN)
AF:
AC:
9234
AN:
10586
Middle Eastern (MID)
AF:
AC:
263
AN:
294
European-Non Finnish (NFE)
AF:
AC:
63358
AN:
67998
Other (OTH)
AF:
AC:
1719
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
1002
2004
3007
4009
5011
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
858
1716
2574
3432
4290
<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:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1809
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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