Variant 12-11267839-C-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.410G>A(p.Arg137His) 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 4)

Exomes 𝑓: 0.00078 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

PRB3
NM_001394862.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.11

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=0.017229706).

BP6

Variant 12-11267839-C-T is Benign according to our data. Variant chr12-11267839-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642712.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRB3	NM_001394862.1 linkuse as main transcript	c.410G>A	p.Arg137His	missense_variant	3/4	ENST00000538488.3
LOC107987435	XR_007063209.1 linkuse as main transcript	n.761-9631C>T		intron_variant, non_coding_transcript_variant
PRB3	NM_006249.5 linkuse as main transcript	c.410G>A	p.Arg137His	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRB3	ENST00000538488.3 linkuse as main transcript	c.410G>A	p.Arg137His	missense_variant	3/4	5	NM_001394862.1	P1
PRB3	ENST00000539835.1 linkuse as main transcript	n.417G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

10990

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000418

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00500

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000534

AC:

AN:

144154

Hom.:

AF XY:

0.000468

AC XY:

AN XY:

78986

show subpopulations

Gnomad AFR exome

AF:

0.000963

Gnomad AMR exome

AF:

0.000685

Gnomad ASJ exome

AF:

0.00216

Gnomad EAS exome

AF:

0.00274

Gnomad SAS exome

AF:

0.000345

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000156

Gnomad OTH exome

AF:

0.000697

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000777

AC:

264

AN:

339868

Hom.:

Cov.:

AF XY:

0.000732

AC XY:

136

AN XY:

185724

show subpopulations

Gnomad4 AFR exome

AF:

0.00110

Gnomad4 AMR exome

AF:

0.000652

Gnomad4 ASJ exome

AF:

0.00211

Gnomad4 EAS exome

AF:

0.00262

Gnomad4 SAS exome

AF:

0.00125

Gnomad4 FIN exome

AF:

0.000147

Gnomad4 NFE exome

AF:

0.000450

Gnomad4 OTH exome

AF:

0.00110

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000454

AC:

AN:

11006

Hom.:

Cov.:

AF XY:

0.000185

AC XY:

AN XY:

5416

show subpopulations

Gnomad4 AFR

AF:

0.000415

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00500

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000443

Hom.:

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

Mar 01, 2024

PRB3: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

Cadd

Benign

3.1

Dann

Benign

0.37

DEOGEN2

Benign

0.022

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00076

M_CAP

Benign

0.00056

MetaRNN

Benign

0.017

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.0070

Sift4G

Benign

0.087

T;T

Vest4

0.12

MVP

0.014

MPC

0.41

ClinPred

0.011

GERP RS

-1.4

gMVP

0.13

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