rs3024718

Positions:

• chr13-113159539-A-G

Variant summary

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

The NM_003891.3(PROZ):​c.71-475A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,048 control chromosomes in the GnomAD database, including 2,648 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 0.18 (2648 hom., cov: 32)
• Consequence: PROZ NM_003891.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173

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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROZ	NM_003891.3	c.71-475A>G		intron_variant		ENST00000375547.7	NP_003882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROZ	ENST00000375547.7	c.71-475A>G		intron_variant		1	NM_003891.3	ENSP00000364697	P2
PROZ	ENST00000342783.5	c.136+275A>G		intron_variant		1		ENSP00000344458	A2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26751 AN: 151928 Hom.: 2651 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0650

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.167

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.176 AC: 26770 AN: 152048 Hom.: 2648 Cov.: 32 AF XY: 0.183 AC XY: 13623 AN XY: 74312

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.170

Alfa AF: 0.171 Hom.: 3991

Bravo AF: 0.166

Asia WGS AF: 0.416 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3024718; hg19: chr13-113813853;