Variant chr12-11393212-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006248.4(PRB2):c.866A>T(p.Gln289Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000262 in 1,450,022 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 14)

Exomes 𝑓: 0.000026 ( 1 hom. )

Consequence

PRB2
NM_006248.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.137

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06035486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRB2	NM_006248.4 linkuse as main transcript	c.866A>T	p.Gln289Leu	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.866A>T	p.Gln289Leu	missense_variant	3/4	5	NM_006248.4	ENSP00000374013.4		P02812

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249316

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135242

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000262

AC:

AN:

1450022

Hom.:

Cov.:

AF XY:

0.0000208

AC XY:

AN XY:

720962

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000326

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

Cov.:

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

Nov 16, 2022

The c.866A>T (p.Q289L) alteration is located in exon 3 (coding exon 3) of the PRB2 gene. This alteration results from a A to T substitution at nucleotide position 866, causing the glutamine (Q) at amino acid position 289 to be replaced by a leucine (L). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.35

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0038

M_CAP

Benign

0.00077

MetaRNN

Benign

0.060

MetaSVM

Benign

-0.99

PROVEAN

Benign

-1.6

REVEL

Benign

0.030

Sift4G

Benign

0.23

Vest4

0.14

MutPred

0.43

Gain of catalytic residue at P286 (P = 0);

MVP

0.11

MPC

0.065

ClinPred

0.061

GERP RS

-2.8

gMVP

0.14

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