rs3024719

Positions:

• chr13-113159911-G-A
• chr13-113159911-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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480

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=-0.95).
• 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/exons	MANE	Protein	UniProt
PROZ	NM_003891.3	c.71-103G>A		intron_variant		ENST00000375547.7	NP_003882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROZ	ENST00000375547.7	c.71-103G>A		intron_variant		1	NM_003891.3	ENSP00000364697	P2
PROZ	ENST00000342783.5	c.137-103G>A		intron_variant		1		ENSP00000344458	A2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22131 AN: 152142 Hom.: 2225 Cov.: 32

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

Gnomad4 AFR exome AF: 0.0285

Gnomad4 AMR exome AF: 0.246

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.312

Gnomad4 SAS exome AF: 0.385

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.145 AC: 22129 AN: 152260 Hom.: 2217 Cov.: 32 AF XY: 0.153 AC XY: 11383 AN XY: 74442

Gnomad4 AFR AF: 0.0315

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.147

Alfa AF: 0.0960 Hom.: 162

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
DANN	Benign	0.67

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: rs3024719; hg19: chr13-113814225;