13-113160093-C-G

Position:

• chr13-113160093-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003891.3(PROZ):​c.150C>G​(p.Phe50Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PROZ NM_003891.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.64

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08305609).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROZ	NM_003891.3	c.150C>G	p.Phe50Leu	missense_variant	2/8	ENST00000375547.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROZ	ENST00000375547.7	c.150C>G	p.Phe50Leu	missense_variant	2/8	1	NM_003891.3	P2
PROZ	ENST00000342783.5	c.216C>G	p.Phe72Leu	missense_variant	3/9	1		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2024

The c.150C>G (p.F50L) alteration is located in exon 2 (coding exon 2) of the PROZ gene. This alteration results from a C to G substitution at nucleotide position 150, causing the phenylalanine (F) at amino acid position 50 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	0.26
DANN	Benign	0.40
DEOGEN2	Uncertain	0.63	.;D
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.68	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.083	T;T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	0.21	.;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.39	N;N
REVEL	Uncertain	0.30
Sift	Benign	0.61	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0070	B;B
Vest4		0.15
MutPred		0.47		.;Loss of loop (P = 0.0374);
MVP		0.87
MPC		0.17
ClinPred		0.048	T
GERP RS		-5.7
Varity_R		0.082
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-113814407;