rs3024735

Positions:

• chr13-113165199-G-A
• chr13-113165199-G-T

Variant summary

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

The NM_003891.3(PROZ):​c.573+79G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,441,546 control chromosomes in the GnomAD database, including 42,105 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 0.20 (3923 hom., cov: 33)
  • Exomes 𝑓: 0.23 (38182 hom.)
• Consequence: PROZ NM_003891.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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]

PCID2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROZ	NM_003891.3	c.573+79G>A		intron_variant		ENST00000375547.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROZ	ENST00000375547.7	c.573+79G>A		intron_variant		1	NM_003891.3	P2
PROZ	ENST00000342783.5	c.639+79G>A		intron_variant		1		A2
PROZ	ENST00000493630.1	n.194+79G>A		intron_variant, non_coding_transcript_variant		5
	ENST00000600642.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30539 AN: 151964 Hom.: 3926 Cov.: 33

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.228 AC: 294273 AN: 1289464 Hom.: 38182 Cov.: 19 AF XY: 0.234 AC XY: 151811 AN XY: 648160

Gnomad4 AFR exome AF: 0.0827

Gnomad4 AMR exome AF: 0.360

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.506

Gnomad4 SAS exome AF: 0.408

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.201 AC: 30562 AN: 152082 Hom.: 3923 Cov.: 33 AF XY: 0.210 AC XY: 15629 AN XY: 74326

Gnomad4 AFR AF: 0.0868

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.210

Alfa AF: 0.194 Hom.: 789

Bravo AF: 0.195

Asia WGS AF: 0.495 AC: 1717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.13
DANN	Benign	0.57

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

LitVar

Other links and lift over

dbSNP: rs3024735; hg19: chr13-113819513;