Genetic Variant NM_001394862.1:c.431C>A (chr12-11267818-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001394862.1(PRB3):c.431C>A(p.Pro144Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0049 ( 0 hom., cov: 4)

Exomes 𝑓: 0.0080 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

PRB3
NM_001394862.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00300

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0096514225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRB3	NM_001394862.1 link	c.431C>A	p.Pro144Gln	missense_variant	Exon 3 of 4	ENST00000538488.3	NP_001381791.1
PRB3	NM_006249.5 link	c.431C>A	p.Pro144Gln	missense_variant	Exon 3 of 5		NP_006240.4	A0A0G2JNB4
LOC107987435	XR_007063209.1 link	n.761-9652G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRB3	ENST00000538488.3 link	c.431C>A	p.Pro144Gln	missense_variant	Exon 3 of 4	5	NM_001394862.1	ENSP00000442626.2		F5H7C1
PRB3	ENST00000539835.1 link	n.438C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.00492

AC:

AN:

6706

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000597

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00153

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.00584

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00838

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00752

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000974

AC:

135

AN:

138674

Hom.:

AF XY:

0.00103

AC XY:

AN XY:

74804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00108

Gnomad EAS exome

AF:

0.00228

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00414

Gnomad NFE exome

AF:

0.000659

Gnomad OTH exome

AF:

0.000664

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00798

AC:

2750

AN:

344748

Hom.:

Cov.:

AF XY:

0.00770

AC XY:

1411

AN XY:

183170

show subpopulations

Gnomad4 AFR exome

AF:

0.000705

Gnomad4 AMR exome

AF:

0.00333

Gnomad4 ASJ exome

AF:

0.00998

Gnomad4 EAS exome

AF:

0.00426

Gnomad4 SAS exome

AF:

0.000899

Gnomad4 FIN exome

AF:

0.0193

Gnomad4 NFE exome

AF:

0.00873

Gnomad4 OTH exome

AF:

0.00758

GnomAD4 genome

AF:

0.00492

AC:

AN:

6712

Hom.:

Cov.:

AF XY:

0.00491

AC XY:

AN XY:

3462

show subpopulations

Gnomad4 AFR

AF:

0.000595

Gnomad4 AMR

AF:

0.00152

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.00584

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00838

Gnomad4 NFE

AF:

0.00752

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0124

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 16, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.431C>A (p.P144Q) alteration is located in exon 3 (coding exon 3) of the PRB3 gene. This alteration results from a C to A substitution at nucleotide position 431, causing the proline (P) at amino acid position 144 to be replaced by a glutamine (Q). 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

-0.45

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.15

DANN

Benign

0.15

DEOGEN2

Benign

0.078

T;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.017

M_CAP

Benign

0.0011

MetaRNN

Benign

0.0097

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.061

Sift4G

Uncertain

0.0060

D;D

Vest4

0.22

MVP

0.048

MPC

0.31

ClinPred

0.52

GERP RS

0.14

gMVP

0.27

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