Genetic Variant PRB3:p.Arg137His (chr12-11267839-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001394862.1(PRB3):c.410G>A(p.Arg137His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 4)

Exomes 𝑓: 0.00078 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

PRB3
NM_001394862.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.11

Publications

8 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017229706).

BP6

Variant 12-11267839-C-T is Benign according to our data. Variant chr12-11267839-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2642712.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394862.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRB3	NM_001394862.1	MANE Select	c.410G>A	p.Arg137His	missense	Exon 3 of 4	NP_001381791.1	Q04118
	PRB3	NM_006249.5		c.410G>A	p.Arg137His	missense	Exon 3 of 5	NP_006240.4	A0A0G2JNB4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRB3	ENST00000538488.3	TSL:5 MANE Select	c.410G>A	p.Arg137His	missense	Exon 3 of 4	ENSP00000442626.2	Q04118
	PRB3	ENST00000539835.1	TSL:2	n.417G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.000455

AC:

AN:

10990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000418

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00500

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000534

AC:

AN:

144154

AF XY:

0.000468

show subpopulations

Gnomad AFR exome

AF:

0.000963

Gnomad AMR exome

AF:

0.000685

Gnomad ASJ exome

AF:

0.00216

Gnomad EAS exome

AF:

0.00274

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000156

Gnomad OTH exome

AF:

0.000697

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000777

AC:

264

AN:

339868

Hom.:

Cov.:

AF XY:

0.000732

AC XY:

136

AN XY:

185724

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00110

AC:

AN:

8198

American (AMR)

AF:

0.000652

AC:

AN:

15334

Ashkenazi Jewish (ASJ)

AF:

0.00211

AC:

AN:

8044

East Asian (EAS)

AF:

0.00262

AC:

AN:

25596

South Asian (SAS)

AF:

0.00125

AC:

AN:

39348

European-Finnish (FIN)

AF:

0.000147

AC:

AN:

33982

Middle Eastern (MID)

AF:

0.00171

AC:

AN:

1168

European-Non Finnish (NFE)

AF:

0.000450

AC:

AN:

190998

Other (OTH)

AF:

0.00110

AC:

AN:

17200

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.323

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000454

AC:

AN:

11006

Hom.:

Cov.:

AF XY:

0.000185

AC XY:

AN XY:

5416

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000415

AC:

AN:

2408

American (AMR)

AF:

0.00

AC:

AN:

810

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

342

East Asian (EAS)

AF:

0.00500

AC:

AN:

800

South Asian (SAS)

AF:

0.00

AC:

AN:

198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

5660

Other (OTH)

AF:

0.00

AC:

AN:

128

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000736447), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.355

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000443

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

CADD

Benign

3.1

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.022

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00076

M_CAP

Benign

0.00056

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.97

PhyloP100

-3.1

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.4

REVEL

Benign

0.0070

Sift4G

Benign

0.087

Vest4

0.12

MVP

0.014

MPC

0.41

ClinPred

0.011

GERP RS

-1.4

gMVP

0.13

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over