Variant 12-11267418-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001394862.1(PRB3):c.831A>C(p.Lys277Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.000016 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000038 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRB3
NM_001394862.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -8.65

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.087258965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRB3	NM_001394862.1 linkuse as main transcript	c.831A>C	p.Lys277Asn	missense_variant	3/4	ENST00000538488.3
LOC107987435	XR_007063209.1 linkuse as main transcript	n.761-10052T>G		intron_variant, non_coding_transcript_variant
PRB3	NM_006249.5 linkuse as main transcript	c.705A>C	p.Lys235Asn	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRB3	ENST00000538488.3 linkuse as main transcript	c.831A>C	p.Lys277Asn	missense_variant	3/4	5	NM_001394862.1	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

122092

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000819

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000339

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000378

AC:

AN:

1242906

Hom.:

Cov.:

AF XY:

0.0000456

AC XY:

AN XY:

614008

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000263

Gnomad4 ASJ exome

AF:

0.000208

Gnomad4 EAS exome

AF:

0.000130

Gnomad4 SAS exome

AF:

0.0000131

Gnomad4 FIN exome

AF:

0.0000839

Gnomad4 NFE exome

AF:

0.0000320

Gnomad4 OTH exome

AF:

0.0000846

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000164

AC:

AN:

122230

Hom.:

Cov.:

AF XY:

0.0000337

AC XY:

AN XY:

59358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000818

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000339

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Jul 14, 2021

The c.705A>C (p.K235N) alteration is located in exon 4 (coding exon 4) of the PRB3 gene. This alteration results from a A to C substitution at nucleotide position 705, causing the lysine (K) at amino acid position 235 to be replaced by an asparagine (N). 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

-0.23

BayesDel_noAF

Benign

-0.57

Cadd

Benign

0.036

Dann

Benign

0.57

DEOGEN2

Benign

0.028

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0013

M_CAP

Benign

0.00020

MetaRNN

Benign

0.087

T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.016

Sift4G

Benign

0.35

T;T

Vest4

0.092

MutPred

0.43

Gain of catalytic residue at P240 (P = 4e-04);.;

MVP

0.014

MPC

0.39

ClinPred

0.078

GERP RS

-2.5

gMVP

0.10

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over