Genetic Variant PRB3:p.Pro186Arg (chr12-11267692-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001394862.1(PRB3):c.557C>G(p.Pro186Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000055 ( 0 hom., cov: 12)

Exomes 𝑓: 0.000018 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRB3
NM_001394862.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.663

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.049610227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRB3	NM_001394862.1 link	c.557C>G	p.Pro186Arg	missense_variant	Exon 3 of 4	ENST00000538488.3	NP_001381791.1
PRB3	NM_006249.5 link	c.557C>G	p.Pro186Arg	missense_variant	Exon 3 of 5		NP_006240.4	A0A0G2JNB4
LOC107987435	XR_007063209.1 link	n.761-9778G>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRB3	ENST00000538488.3 link	c.557C>G	p.Pro186Arg	missense_variant	Exon 3 of 4	5	NM_001394862.1	ENSP00000442626.2		F5H7C1
PRB3	ENST00000539835.1 link	n.*88C>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000551

AC:

AN:

90752

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000117

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000456

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000211

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000632

AC:

AN:

237158

Hom.:

AF XY:

0.0000387

AC XY:

AN XY:

129110

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000284

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000692

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000275

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000179

AC:

AN:

1399066

Hom.:

Cov.:

AF XY:

0.0000158

AC XY:

AN XY:

695720

show subpopulations

Gnomad4 AFR exome

AF:

0.0000336

Gnomad4 AMR exome

AF:

0.000374

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000262

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000466

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

AF:

0.0000551

AC:

AN:

90752

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

44064

show subpopulations

Gnomad4 AFR

AF:

0.000117

Gnomad4 AMR

AF:

0.000103

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000456

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000211

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000486

Hom.:

ExAC

AF:

0.00000837

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.49

CADD

Benign

4.6

DANN

Benign

0.044

DEOGEN2

Benign

0.029

T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.0079

M_CAP

Benign

0.00064

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.053

Sift4G

Benign

0.099

T;T

Vest4

0.20

MutPred

0.35

Gain of catalytic residue at P187 (P = 0);Gain of catalytic residue at P187 (P = 0);

MVP

0.13

MPC

0.35

ClinPred

0.37

GERP RS

1.2

gMVP

0.50

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over