Variant 12-11267692-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001394862.1(PRB3):c.557C>A(p.Pro186Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 12)

Exomes 𝑓: 0.00015 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

PRB3
NM_001394862.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005709827).

BP6

Variant 12-11267692-G-T is Benign according to our data. Variant chr12-11267692-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642709.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRB3	NM_001394862.1 linkuse as main transcript	c.557C>A	p.Pro186Gln	missense_variant	3/4	ENST00000538488.3	NP_001381791.1
PRB3	NM_006249.5 linkuse as main transcript	c.557C>A	p.Pro186Gln	missense_variant	3/5		NP_006240.4	A0A0G2JNB4
LOC107987435	XR_007063209.1 linkuse as main transcript	n.761-9778G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRB3	ENST00000538488.3 linkuse as main transcript	c.557C>A	p.Pro186Gln	missense_variant	3/4	5	NM_001394862.1	ENSP00000442626.2		F5H7C1

Frequencies

GnomAD3 genomes

AF:

0.000540

AC:

AN:

90718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000527

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00330

Gnomad SAS

AF:

0.000456

Gnomad FIN

AF:

0.00125

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000274

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000455

AC:

108

AN:

237158

Hom.:

AF XY:

0.000356

AC XY:

AN XY:

129110

show subpopulations

Gnomad AFR exome

AF:

0.000220

Gnomad AMR exome

AF:

0.0000945

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00515

Gnomad SAS exome

AF:

0.0000692

Gnomad FIN exome

AF:

0.000141

Gnomad NFE exome

AF:

0.0000642

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000145

AC:

203

AN:

1398750

Hom.:

Cov.:

AF XY:

0.000145

AC XY:

101

AN XY:

695574

show subpopulations

Gnomad4 AFR exome

AF:

0.000168

Gnomad4 AMR exome

AF:

0.000249

Gnomad4 ASJ exome

AF:

0.000167

Gnomad4 EAS exome

AF:

0.00270

Gnomad4 SAS exome

AF:

0.0000872

Gnomad4 FIN exome

AF:

0.000269

Gnomad4 NFE exome

AF:

0.0000420

Gnomad4 OTH exome

AF:

0.000261

GnomAD4 genome

AF:

0.000529

AC:

AN:

90754

Hom.:

Cov.:

AF XY:

0.000703

AC XY:

AN XY:

44098

show subpopulations

Gnomad4 AFR

AF:

0.000526

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00301

Gnomad4 SAS

AF:

0.000457

Gnomad4 FIN

AF:

0.00125

Gnomad4 NFE

AF:

0.000274

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000670

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

PRB3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

3.7

DANN

Benign

0.23

DEOGEN2

Benign

0.030

T;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0081

MetaRNN

Benign

0.0057

T;T

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.31

N;N

REVEL

Benign

0.032

Sift4G

Uncertain

0.024

D;D

Vest4

0.19

MVP

0.048

MPC

0.31

ClinPred

0.022

GERP RS

1.2

gMVP

0.46

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