Variant 12-11267453-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBS2_Supporting

The NM_001394862.1(PRB3):c.796A>G(p.Lys266Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,535,148 control chromosomes in the GnomAD database, including 182 homozygotes. 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 0.00050 ( 10 hom., cov: 19)

Exomes 𝑓: 0.0031 ( 172 hom. )

Consequence

PRB3
NM_001394862.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.79

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 Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007795185).

BP6

Variant 12-11267453-T-C is Benign according to our data. Variant chr12-11267453-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2642707.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 10 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	UniProt
PRB3	NM_001394862.1 linkuse as main transcript	c.796A>G	p.Lys266Glu	missense_variant	3/4	ENST00000538488.3	NP_001381791.1
PRB3	NM_006249.5 linkuse as main transcript	c.670A>G	p.Lys224Glu	missense_variant	4/5		NP_006240.4	A0A0G2JNB4
LOC107987435	XR_007063209.1 linkuse as main transcript	n.761-10017T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRB3	ENST00000538488.3 linkuse as main transcript	c.796A>G	p.Lys266Glu	missense_variant	3/4	5	NM_001394862.1	ENSP00000442626.2		F5H7C1

Frequencies

GnomAD3 genomes

AF:

0.000497

AC:

AN:

140928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000704

Gnomad ASJ

AF:

0.00120

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000763

Gnomad OTH

AF:

0.000522

GnomAD3 exomes

AF:

0.000711

AC:

177

AN:

248832

Hom.:

AF XY:

0.000756

AC XY:

102

AN XY:

134942

show subpopulations

Gnomad AFR exome

AF:

0.000259

Gnomad AMR exome

AF:

0.000609

Gnomad ASJ exome

AF:

0.00150

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000493

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00102

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.00306

AC:

4270

AN:

1394100

Hom.:

172

Cov.:

AF XY:

0.00292

AC XY:

2015

AN XY:

690718

show subpopulations

Gnomad4 AFR exome

AF:

0.000493

Gnomad4 AMR exome

AF:

0.000840

Gnomad4 ASJ exome

AF:

0.00135

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000409

Gnomad4 FIN exome

AF:

0.0000612

Gnomad4 NFE exome

AF:

0.00372

Gnomad4 OTH exome

AF:

0.00266

GnomAD4 genome

AF:

0.000496

AC:

AN:

141048

Hom.:

Cov.:

AF XY:

0.000453

AC XY:

AN XY:

68406

show subpopulations

Gnomad4 AFR

AF:

0.000104

Gnomad4 AMR

AF:

0.000703

Gnomad4 ASJ

AF:

0.00120

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000207

Gnomad4 NFE

AF:

0.000763

Gnomad4 OTH

AF:

0.000516

Alfa

AF:

0.000510

Hom.:

ESP6500AA

AF:

0.000689

AC:

ESP6500EA

AF:

0.00550

AC:

ExAC

AF:

0.00138

AC:

129

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

Jul 01, 2024

PRB3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.5

DANN

Benign

0.45

DEOGEN2

Benign

0.023

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0011

M_CAP

Benign

0.00029

MetaRNN

Benign

0.0078

T;T

MetaSVM

Benign

-0.95

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.033

Sift4G

Benign

0.49

T;T

Vest4

0.11

MVP

0.030

MPC

0.46

ClinPred

0.0093

GERP RS

-2.5

gMVP

0.33

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