chr13-113160128-T-C

Variant names:

• chr13-113160128-T-C
• NM_003891.3:c.185T>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003891.3(PROZ):​c.185T>C​(p.Ile62Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PROZ NM_003891.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29771724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROZ	NM_003891.3	c.185T>C	p.Ile62Thr	missense_variant	Exon 2 of 8	ENST00000375547.7	NP_003882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROZ	ENST00000375547.7	c.185T>C	p.Ile62Thr	missense_variant	Exon 2 of 8	1	NM_003891.3	ENSP00000364697.2
PROZ	ENST00000342783.5	c.251T>C	p.Ile84Thr	missense_variant	Exon 3 of 9	1		ENSP00000344458.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461812 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	16
DANN	Benign	0.54
DEOGEN2	Uncertain	0.61	.;D
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.81	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Uncertain	0.67	D
MutationAssessor	Benign	1.4	.;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.34	N;N
REVEL	Uncertain	0.36
Sift	Benign	0.43	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.059	B;B
Vest4		0.33
MutPred		0.56		.;Loss of stability (P = 0.0343);
MVP		0.84
MPC		0.53
ClinPred		0.15	T
GERP RS		1.4
Varity_R		0.12
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-113814442;