Variant 20-35174893-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006404.5(PROCR):c.262T>C(p.Ser88Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000979 in 1,609,320 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 29)

Exomes 𝑓: 0.00097 ( 16 hom. )

Consequence

PROCR
NM_006404.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.93

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010937989).

BP6

Variant 20-35174893-T-C is Benign according to our data. Variant chr20-35174893-T-C is described in ClinVar as [Benign]. Clinvar id is 731572.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROCR	NM_006404.5 linkuse as main transcript	c.262T>C	p.Ser88Pro	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.262T>C	p.Ser88Pro	missense_variant	2/4	1	NM_006404.5	ENSP00000216968.3	Q9UNN8
PROCR	ENST00000635377.1 linkuse as main transcript	c.160T>C	p.Ser54Pro	missense_variant	1/4	5		ENSP00000489117.1	A0A0U1RQQ4
ENSG00000278367	ENST00000615962.1 linkuse as main transcript	n.27A>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

164

AN:

151332

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000395

Gnomad ASJ

AF:

0.0350

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.00241

GnomAD3 exomes

AF:

0.00186

AC:

444

AN:

238974

Hom.:

AF XY:

0.00188

AC XY:

244

AN XY:

129768

show subpopulations

Gnomad AFR exome

AF:

0.0000649

Gnomad AMR exome

AF:

0.000540

Gnomad ASJ exome

AF:

0.0370

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.00291

GnomAD4 exome

AF:

0.000968

AC:

1412

AN:

1457988

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

765

AN XY:

725096

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000546

Gnomad4 ASJ exome

AF:

0.0371

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000236

Gnomad4 OTH exome

AF:

0.00259

GnomAD4 genome

AF:

0.00108

AC:

164

AN:

151332

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

73848

show subpopulations

Gnomad4 AFR

AF:

0.000146

Gnomad4 AMR

AF:

0.000395

Gnomad4 ASJ

AF:

0.0350

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00241

Alfa

AF:

0.00199

Hom.:

Bravo

AF:

0.00128

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00128

AC:

155

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.049

DANN

Benign

0.30

DEOGEN2

Benign

0.31

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.19

M_CAP

Benign

0.033

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.29

Sift

Benign

0.28

Sift4G

Benign

0.28

Polyphen

0.078

Vest4

0.24

MVP

0.41

MPC

0.56

ClinPred

0.014

GERP RS

-10

Varity_R

0.46

gMVP

0.62

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