rs3024718

Variant names:

• chr13-113159539-A-G
• rs3024718
• NM_003891.3:c.71-475A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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 deficiency

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PROZ	NM_003891.3	c.71-475A>G		intron_variant	Intron 1 of 7	ENST00000375547.7	NP_003882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROZ	ENST00000375547.7	c.71-475A>G		intron_variant	Intron 1 of 7	1	NM_003891.3	ENSP00000364697.2
PROZ	ENST00000342783.5	c.136+275A>G		intron_variant	Intron 2 of 8	1		ENSP00000344458.4

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

African (AFR) AF: 0.135 AC: 5590 AN: 41472

American (AMR) AF: 0.183 AC: 2796 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3466

East Asian (EAS) AF: 0.333 AC: 1717 AN: 5156

South Asian (SAS) AF: 0.404 AC: 1947 AN: 4816

European-Finnish (FIN) AF: 0.224 AC: 2366 AN: 10582

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11494 AN: 67970

Other (OTH) AF: 0.170 AC: 358 AN: 2112

Alfa AF: 0.173 Hom.: 10080

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
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3024718; hg19: chr13-113813853;