Variant 12-11267429-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001394862.1(PRB3):c.820G>A(p.Gly274Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000459 in 1,567,270 control chromosomes in the GnomAD database, including 24 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 4 hom., cov: 25)

Exomes 𝑓: 0.00048 ( 20 hom. )

Consequence

PRB3
NM_001394862.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.036661386).

BS2

High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRB3	NM_001394862.1 linkuse as main transcript	c.820G>A	p.Gly274Arg	missense_variant	3/4	ENST00000538488.3
LOC107987435	XR_007063209.1 linkuse as main transcript	n.761-10041C>T		intron_variant, non_coding_transcript_variant
PRB3	NM_006249.5 linkuse as main transcript	c.694G>A	p.Gly232Arg	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRB3	ENST00000538488.3 linkuse as main transcript	c.820G>A	p.Gly274Arg	missense_variant	3/4	5	NM_001394862.1	P1

Frequencies

GnomAD3 genomes

AF:

0.000275

AC:

AN:

145596

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000406

Gnomad ASJ

AF:

0.000592

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000996

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000472

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000230

AC:

AN:

248308

Hom.:

AF XY:

0.000230

AC XY:

AN XY:

134654

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.000300

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000338

Gnomad OTH exome

AF:

0.000498

GnomAD4 exome

AF:

0.000478

AC:

680

AN:

1421674

Hom.:

Cov.:

AF XY:

0.000453

AC XY:

319

AN XY:

704758

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.000319

Gnomad4 ASJ exome

AF:

0.000198

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000380

Gnomad4 FIN exome

AF:

0.0000792

Gnomad4 NFE exome

AF:

0.000567

Gnomad4 OTH exome

AF:

0.000496

GnomAD4 genome

AF:

0.000275

AC:

AN:

145596

Hom.:

Cov.:

AF XY:

0.000339

AC XY:

AN XY:

70782

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000406

Gnomad4 ASJ

AF:

0.000592

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000996

Gnomad4 NFE

AF:

0.000472

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000491

Hom.:

ESP6500AA

AF:

0.000229

AC:

ESP6500EA

AF:

0.000583

AC:

ExAC

AF:

0.000582

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2024

The c.694G>A (p.G232R) alteration is located in exon 4 (coding exon 4) of the PRB3 gene. This alteration results from a G to A substitution at nucleotide position 694, causing the glycine (G) at amino acid position 232 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.28

Cadd

Benign

Dann

Benign

0.38

DEOGEN2

Benign

0.028

T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0032

M_CAP

Benign

0.00056

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-0.90

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.054

Sift4G

Uncertain

0.031

D;T

Vest4

0.11

MutPred

0.33

Gain of catalytic residue at P228 (P = 5e-04);.;

MVP

0.16

MPC

0.39

ClinPred

0.039

GERP RS

0.068

gMVP

0.089

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