NM_003891.3:c.573+79G>A

Variant names:

• chr13-113165199-G-A
• rs3024735
• NM_003891.3:c.573+79G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003891.3(PROZ):​c.573+79G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,441,546 control chromosomes in the GnomAD database, including 42,105 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 0.20 (3923 hom., cov: 33)
  • Exomes 𝑓: 0.23 (38182 hom.)
• Consequence: PROZ NM_003891.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 23 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]

PCID2 (HGNC:25653): (PCI domain containing 2) This gene encodes a component of the TREX-2 complex (transcription and export complex 2), which regulates mRNA export from the nucleus. This protein regulates expression of Mad2 mitotic arrest deficient-like 1, a cell division checkpoint protein. This protein also interacts with and stabilizes Brca2 (breast cancer 2) protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ENSG00000269125 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROZ	NM_003891.3	c.573+79G>A		intron_variant	Intron 6 of 7	ENST00000375547.7	NP_003882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROZ	ENST00000375547.7	c.573+79G>A		intron_variant	Intron 6 of 7	1	NM_003891.3	ENSP00000364697.2
PROZ	ENST00000342783.5	c.639+79G>A		intron_variant	Intron 7 of 8	1		ENSP00000344458.4
PROZ	ENST00000493630.1	n.194+79G>A		intron_variant	Intron 2 of 4	5
ENSG00000269125	ENST00000600642.1	n.-16C>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30539 AN: 151964 Hom.: 3926 Cov.: 33

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.228 AC: 294273 AN: 1289464 Hom.: 38182 Cov.: 19 AF XY: 0.234 AC XY: 151811 AN XY: 648160

African (AFR) AF: 0.0827 AC: 2484 AN: 30028

American (AMR) AF: 0.360 AC: 14859 AN: 41292

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 4532 AN: 24968

East Asian (EAS) AF: 0.506 AC: 19392 AN: 38306

South Asian (SAS) AF: 0.408 AC: 33264 AN: 81432

European-Finnish (FIN) AF: 0.230 AC: 8897 AN: 38602

Middle Eastern (MID) AF: 0.179 AC: 906 AN: 5050

European-Non Finnish (NFE) AF: 0.202 AC: 197223 AN: 974712

Other (OTH) AF: 0.231 AC: 12716 AN: 55074

GnomAD4 genome AF: 0.201 AC: 30562 AN: 152082 Hom.: 3923 Cov.: 33 AF XY: 0.210 AC XY: 15629 AN XY: 74326

African (AFR) AF: 0.0868 AC: 3603 AN: 41490

American (AMR) AF: 0.273 AC: 4181 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3466

East Asian (EAS) AF: 0.549 AC: 2832 AN: 5156

South Asian (SAS) AF: 0.427 AC: 2053 AN: 4812

European-Finnish (FIN) AF: 0.248 AC: 2617 AN: 10562

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13993 AN: 67976

Other (OTH) AF: 0.210 AC: 444 AN: 2116

Alfa AF: 0.194 Hom.: 789

Bravo AF: 0.195

Asia WGS AF: 0.495 AC: 1717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.13
DANN	Benign	0.57
PhyloP100		-1.3
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: rs3024735; hg19: chr13-113819513;