Variant 20-35174718-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006404.5(PROCR):c.87T>G(p.His29Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

PROCR
NM_006404.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.165

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROCR	NM_006404.5 link	c.87T>G	p.His29Gln	missense_variant	Exon 2 of 4	ENST00000216968.5	NP_006395.2	Q9UNN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PROCR	ENST00000216968.5 link	c.87T>G	p.His29Gln	missense_variant	Exon 2 of 4	1	NM_006404.5	ENSP00000216968.3	Q9UNN8
ENSG00000278367	ENST00000615962.1 link	n.202A>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
PROCR	ENST00000635377.1 link	c.-16T>G		upstream_gene_variant		5		ENSP00000489117.1	A0A0U1RQQ4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250950

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135686

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727236

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.87T>G (p.H29Q) alteration is located in exon 2 (coding exon 2) of the PROCR gene. This alteration results from a T to G substitution at nucleotide position 87, causing the histidine (H) at amino acid position 29 to be replaced by a glutamine (Q). 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

Benign

0.21

BayesDel_addAF

Benign

-0.0025

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.24

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.38

M_CAP

Uncertain

0.088

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.35

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.46

Sift

Benign

0.058

Sift4G

Benign

0.45

Polyphen

0.96

Vest4

0.32

MutPred

0.62

Loss of catalytic residue at L31 (P = 0.0694);

MVP

0.76

MPC

0.45

ClinPred

0.47

GERP RS

2.4

Varity_R

0.36

gMVP

0.33

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