Variant chr12-11392966-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_006248.4(PRB2):c.1112A>C(p.Gln371Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000173 in 1,603,136 control chromosomes in the GnomAD database, including 1 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 1 hom., cov: 19)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

PRB2
NM_006248.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.81

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019273967).

BP6

Variant 12-11392966-T-G is Benign according to our data. Variant chr12-11392966-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2306760.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRB2	NM_006248.4 linkuse as main transcript	c.1112A>C	p.Gln371Pro	missense_variant	3/4	ENST00000389362.6	NP_006239.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRB2	ENST00000389362.6 linkuse as main transcript	c.1112A>C	p.Gln371Pro	missense_variant	3/4	5	NM_006248.4	ENSP00000374013	P1

Frequencies

GnomAD3 genomes

AF:

0.000259

AC:

AN:

142774

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000785

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000138

Gnomad ASJ

AF:

0.000607

Gnomad EAS

AF:

0.000216

Gnomad SAS

AF:

0.000483

Gnomad FIN

AF:

0.0000998

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000401

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000213

AC:

AN:

248846

Hom.:

AF XY:

0.000230

AC XY:

AN XY:

134792

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.000708

Gnomad EAS exome

AF:

0.000273

Gnomad SAS exome

AF:

0.0000990

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000293

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.000164

AC:

240

AN:

1460254

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

115

AN XY:

726382

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000846

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.0000698

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000156

Gnomad4 OTH exome

AF:

0.000498

GnomAD4 genome

AF:

0.000259

AC:

AN:

142882

Hom.:

Cov.:

AF XY:

0.000258

AC XY:

AN XY:

69886

show subpopulations

Gnomad4 AFR

AF:

0.0000783

Gnomad4 AMR

AF:

0.000138

Gnomad4 ASJ

AF:

0.000607

Gnomad4 EAS

AF:

0.000216

Gnomad4 SAS

AF:

0.000483

Gnomad4 FIN

AF:

0.0000998

Gnomad4 NFE

AF:

0.000401

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00153

Hom.:

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000238

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.027

DANN

Benign

0.36

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.000090

M_CAP

Benign

0.00051

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

0.92

REVEL

Benign

0.023

Sift4G

Benign

1.0

Vest4

0.082

MVP

0.014

MPC

0.079

ClinPred

0.024

GERP RS

-2.8

gMVP

0.021

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