Variant 12-11393102-G-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_006248.4(PRB2):c.976C>A(p.Gln326Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000776 in 1,571,694 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 15)

Exomes 𝑓: 0.00080 ( 10 hom. )

Consequence

PRB2
NM_006248.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34

Variant links:

Genes affected

PRB2 (HGNC:9338): (proline rich protein BstNI subfamily 2) This gene encodes a member of the heterogeneous family of basic, proline-rich, human salivary glycoproteins. The encoded preproprotein undergoes proteolytic processing to generate one or more mature isoforms before secretion from the parotid glands. Multiple alleles of this gene exhibiting variations in the length of the tandem repeats, polymorphic cleavage sites and polymorphic stop codons have been identified. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12. [provided by RefSeq, May 2023]

PRB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011890411).

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRB2	NM_006248.4 linkuse as main transcript	c.976C>A	p.Gln326Lys	missense_variant	3/4	ENST00000389362.6	NP_006239.3	P02812

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRB2	ENST00000389362.6 linkuse as main transcript	c.976C>A	p.Gln326Lys	missense_variant	3/4	5	NM_006248.4	ENSP00000374013.4		P02812

Frequencies

GnomAD3 genomes

AF:

0.000462

AC:

AN:

119106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000715

Gnomad ASJ

AF:

0.000669

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00847

Gnomad NFE

AF:

0.000621

Gnomad OTH

AF:

0.00254

GnomAD3 exomes

AF:

0.000909

AC:

217

AN:

238594

Hom.:

AF XY:

0.000950

AC XY:

123

AN XY:

129452

show subpopulations

Gnomad AFR exome

AF:

0.0000680

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.00107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000624

Gnomad FIN exome

AF:

0.0000477

Gnomad NFE exome

AF:

0.00128

Gnomad OTH exome

AF:

0.00156

GnomAD4 exome

AF:

0.000802

AC:

1165

AN:

1452510

Hom.:

Cov.:

AF XY:

0.000826

AC XY:

597

AN XY:

722526

show subpopulations

Gnomad4 AFR exome

AF:

0.000669

Gnomad4 AMR exome

AF:

0.00113

Gnomad4 ASJ exome

AF:

0.00147

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000770

Gnomad4 FIN exome

AF:

0.0000566

Gnomad4 NFE exome

AF:

0.000723

Gnomad4 OTH exome

AF:

0.00177

GnomAD4 genome

AF:

0.000453

AC:

AN:

119184

Hom.:

Cov.:

AF XY:

0.000587

AC XY:

AN XY:

57948

show subpopulations

Gnomad4 AFR

AF:

0.000104

Gnomad4 AMR

AF:

0.000714

Gnomad4 ASJ

AF:

0.000669

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000622

Gnomad4 OTH

AF:

0.00251

Alfa

AF:

0.000843

Hom.:

ESP6500AA

AF:

0.000691

AC:

ESP6500EA

AF:

0.000708

AC:

ExAC

AF:

0.000909

AC:

110

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

Dec 27, 2023

The c.976C>A (p.Q326K) alteration is located in exon 3 (coding exon 3) of the PRB2 gene. This alteration results from a C to A substitution at nucleotide position 976, causing the glutamine (Q) at amino acid position 326 to be replaced by a lysine (K). 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

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.8

DANN

Benign

0.40

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.045

M_CAP

Benign

0.0023

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.97

PROVEAN

Benign

-0.92

REVEL

Benign

0.027

Sift4G

Benign

0.28

Vest4

0.080

MVP

0.040

MPC

0.082

ClinPred

0.014

GERP RS

0.39

gMVP

0.081

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