rs3024711

Variant names:

• chr13-113158954-A-G
• rs3024711
• NM_003891.3:c.70+224A>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.70+224A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 151,156 control chromosomes in the GnomAD database, including 2,388 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 0.16 (2388 hom., cov: 28)
• Consequence: PROZ NM_003891.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 6 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)

ENSG00000304064 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROZ	NM_003891.3	c.70+224A>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.70+224A>G		intron_variant	Intron 1 of 7	1	NM_003891.3	ENSP00000364697.2
PROZ	ENST00000342783.5	c.70+224A>G		intron_variant	Intron 1 of 8	1		ENSP00000344458.4
ENSG00000304064	ENST00000799342.1	n.46T>C		non_coding_transcript_exon_variant	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24598 AN: 151038 Hom.: 2393 Cov.: 28

Gnomad AFR AF: 0.0886

Gnomad AMI AF: 0.0639

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.163 AC: 24614 AN: 151156 Hom.: 2388 Cov.: 28 AF XY: 0.171 AC XY: 12595 AN XY: 73828

African (AFR) AF: 0.0887 AC: 3652 AN: 41160

American (AMR) AF: 0.178 AC: 2707 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 421 AN: 3458

East Asian (EAS) AF: 0.334 AC: 1692 AN: 5064

South Asian (SAS) AF: 0.405 AC: 1927 AN: 4756

European-Finnish (FIN) AF: 0.223 AC: 2328 AN: 10450

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.169 AC: 11459 AN: 67766

Other (OTH) AF: 0.160 AC: 335 AN: 2100

Alfa AF: 0.163 Hom.: 320

Bravo AF: 0.151

Asia WGS AF: 0.410 AC: 1421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.67
PhyloP100		0.034
PromoterAI		-0.0056	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3024711; hg19: chr13-113813268;