rs2273971

Positions:

• chr13-113158648-G-A
• chr13-113158648-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838

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]

ACMG classification

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
PROZ	NM_003891.3	c.-13G>A		5_prime_UTR_variant	1/8	ENST00000375547.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROZ	ENST00000375547.7	c.-13G>A		5_prime_UTR_variant	1/8	1	NM_003891.3	P2
PROZ	ENST00000342783.5	c.-13G>A		5_prime_UTR_variant	1/9	1		A2

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123042 AN: 151862 Hom.: 51322 Cov.: 31

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

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

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

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

Other links and lift over

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