Variant chr20-35174942-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006404.5(PROCR):c.311G>C(p.Arg104Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000564 in 1,418,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

PROCR
NM_006404.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

Variant links:

Genes affected

PROCR (HGNC:9452): (protein C receptor) The protein encoded by this gene is a receptor for activated protein C, a serine protease activated by and involved in the blood coagulation pathway. The encoded protein is an N-glycosylated type I membrane protein that enhances the activation of protein C. Mutations in this gene have been associated with venous thromboembolism and myocardial infarction, as well as with late fetal loss during pregnancy. The encoded protein may also play a role in malarial infection and has been associated with cancer. [provided by RefSeq, Jul 2013]

PROCR links:

MMP24-AS1-EDEM2 (HGNC:):

MMP24-AS1-EDEM2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.919

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROCR	NM_006404.5 linkuse as main transcript	c.311G>C	p.Arg104Pro	missense_variant	2/4	ENST00000216968.5	NP_006395.2	Q9UNN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PROCR	ENST00000216968.5 linkuse as main transcript	c.311G>C	p.Arg104Pro	missense_variant	2/4	1	NM_006404.5	ENSP00000216968.3	Q9UNN8
PROCR	ENST00000635377.1 linkuse as main transcript	c.209G>C	p.Arg70Pro	missense_variant	1/4	5		ENSP00000489117.1	A0A0U1RQQ4
ENSG00000278367	ENST00000615962.1 linkuse as main transcript	n.-23C>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000559

AC:

AN:

178926

Hom.:

AF XY:

0.0000104

AC XY:

AN XY:

96568

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000400

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000564

AC:

AN:

1418390

Hom.:

Cov.:

AF XY:

0.00000712

AC XY:

AN XY:

701792

show subpopulations

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:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000641

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000840

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2022

The c.311G>C (p.R104P) alteration is located in exon 2 (coding exon 2) of the PROCR gene. This alteration results from a G to C substitution at nucleotide position 311, causing the arginine (R) at amino acid position 104 to be replaced by a proline (P). 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

0.90

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.74

M_CAP

Pathogenic

0.29

MetaRNN

Pathogenic

0.92

MetaSVM

Uncertain

0.44

MutationAssessor

Uncertain

2.7

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.5

REVEL

Pathogenic

0.77

Sift

Benign

0.031

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.81

MutPred

0.61

Loss of helix (P = 0.0376);

MVP

0.89

MPC

1.5

ClinPred

0.94

GERP RS

4.3

Varity_R

0.97

gMVP

0.75

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over