Variant rs71455367 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting

The NM_001394862.1(PRB3):c.145C>T(p.Arg49Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,601,000 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 28)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

PRB3
NM_001394862.1 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -1.57

Variant links:

Genes affected

PRB3 (HGNC:9339): (proline rich protein BstNI subfamily 3) This gene encodes a member of the heterogeneous family of basic, proline-rich, human salivary glycoproteins. Multiple alleles of this gene exhibiting variations in the length of the tandem repeats have been identified. The reference genome encodes the "Long" allele. The protein isoforms encoded by this gene are recognized as the "first line of oral defense" against the detrimental effects of polyphenols in the diet and pathogen infections. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12. [provided by RefSeq, Nov 2015]

PRB3 links:

LOC107987435 (HGNC:):

LOC107987435 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP5

Variant 12-11268104-G-A is Pathogenic according to our data. Variant chr12-11268104-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 13733.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053963363). . Strength limited to SUPPORTING due to the PP5.

BS2

High Homozygotes in GnomAdExome4 at 3 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PRB3	NM_001394862.1 linkuse as main transcript	c.145C>T	p.Arg49Cys	missense_variant	3/4	ENST00000538488.3	NP_001381791.1
LOC107987435	XR_007063209.1 linkuse as main transcript	n.761-9366G>A		intron_variant, non_coding_transcript_variant
PRB3	NM_006249.5 linkuse as main transcript	c.145C>T	p.Arg49Cys	missense_variant	3/5		NP_006240.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRB3	ENST00000538488.3 linkuse as main transcript	c.145C>T	p.Arg49Cys	missense_variant	3/4	5	NM_001394862.1	ENSP00000442626	P1
PRB3	ENST00000539835.1 linkuse as main transcript	n.152C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

155

AN:

143688

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000158

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00145

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000463

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000851

Gnomad OTH

AF:

0.00519

GnomAD3 exomes

AF:

0.00135

AC:

336

AN:

249400

Hom.:

AF XY:

0.00132

AC XY:

178

AN XY:

135256

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000901

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000850

Gnomad OTH exome

AF:

0.00248

GnomAD4 exome

AF:

0.00103

AC:

1496

AN:

1457180

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

746

AN XY:

724816

show subpopulations

Gnomad4 AFR exome

AF:

0.0000611

Gnomad4 AMR exome

AF:

0.000920

Gnomad4 ASJ exome

AF:

0.0163

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000830

Gnomad4 OTH exome

AF:

0.00168

GnomAD4 genome

AF:

0.00108

AC:

155

AN:

143820

Hom.:

Cov.:

AF XY:

0.000884

AC XY:

AN XY:

70110

show subpopulations

Gnomad4 AFR

AF:

0.000158

Gnomad4 AMR

AF:

0.00145

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000463

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000851

Gnomad4 OTH

AF:

0.00512

Alfa

AF:

0.00108

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00175

AC:

ExAC

AF:

0.00115

AC:

139

EpiCase

AF:

0.00109

EpiControl

AF:

0.00143

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRB3S(CYS)

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 1990

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.031

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0010

M_CAP

Benign

0.00098

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.041

Sift4G

Uncertain

0.054

T;T

Vest4

0.25

MVP

0.030

MPC

0.45

ClinPred

0.014

GERP RS

-0.37

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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