rs71455367

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -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. 15/19 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

Publications

5 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PRB3	NM_001394862.1 link	c.145C>T	p.Arg49Cys	missense_variant	Exon 3 of 4	ENST00000538488.3	NP_001381791.1
PRB3	NM_006249.5 link	c.145C>T	p.Arg49Cys	missense_variant	Exon 3 of 5		NP_006240.4	A0A0G2JNB4
LOC107987435	XR_007063209.1 link	n.761-9366G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRB3	ENST00000538488.3 link	c.145C>T	p.Arg49Cys	missense_variant	Exon 3 of 4	5	NM_001394862.1	ENSP00000442626.2		F5H7C1
PRB3	ENST00000539835.1 link	n.152C>T		non_coding_transcript_exon_variant	Exon 2 of 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

GnomAD2 exomes

AF:

0.00135

AC:

336

AN:

249400

AF XY:

0.00132

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 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

African (AFR)

AF:

0.0000611

AC:

AN:

32726

American (AMR)

AF:

0.000920

AC:

AN:

44564

Ashkenazi Jewish (ASJ)

AF:

0.0163

AC:

423

AN:

25944

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39562

South Asian (SAS)

AF:

0.0000349

AC:

AN:

85852

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53350

Middle Eastern (MID)

AF:

0.000522

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.000830

AC:

921

AN:

1109326

Other (OTH)

AF:

0.00168

AC:

101

AN:

60106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

106

212

318

424

530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00108

AC:

155

AN:

143820

Hom.:

Cov.:

AF XY:

0.000884

AC XY:

AN XY:

70110

show subpopulations

African (AFR)

AF:

0.000158

AC:

AN:

38078

American (AMR)

AF:

0.00145

AC:

AN:

14480

Ashkenazi Jewish (ASJ)

AF:

0.0176

AC:

AN:

3400

East Asian (EAS)

AF:

0.00

AC:

AN:

4774

South Asian (SAS)

AF:

0.000463

AC:

AN:

4316

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9908

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.000851

AC:

AN:

65772

Other (OTH)

AF:

0.00512

AC:

AN:

1952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Oct 01, 1990

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

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

PhyloP100

-1.6

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

Mutation Taster

=99/1

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over