12-10847181-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_007244.3(PRR4):c.287G>A(p.Arg96Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,612,768 control chromosomes in the GnomAD database, including 268,556 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.49 ( 20668 hom., cov: 29)

Exomes 𝑓: 0.58 ( 247888 hom. )

Consequence

PRR4
NM_007244.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.34

Variant links:

Genes affected

PRR4 (HGNC:18020): (proline rich 4) This gene encodes a member of the proline-rich protein family that lacks a conserved repetitive domain. This protein may play a role in protective functions in the eye. Alternative splicing result in multiple transcript variants. Read-through transcription also exists between this gene and the upstream PRH1 (proline-rich protein HaeIII subfamily 1) gene. [provided by RefSeq, Feb 2011]

PRR4 links:

PRH1-PRR4 (HGNC:):

PRH1-PRR4 links:

PRH1 (HGNC:9366): (proline rich protein HaeIII subfamily 1) This gene encodes a member of the heterogeneous family of proline-rich salivary glycoproteins. The encoded preproprotein undergoes proteolytic processing to generate one or more mature isoforms before secretion from the parotid and submandibular/sublingual glands. Multiple distinct alleles of this locus including the parotid isoelectric-focusing variant slow (PIF-s), the parotid acidic protein (Pa), and the double band slow (Db-s) isoforms have been characterized. The reference genome encodes the Db-s allele. Certain alleles of this gene are associated with susceptibility to dental caries. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12. Co-transcription of this gene with adjacent genes has been observed. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]

PRH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3043367E-6).

BP6

Variant 12-10847181-C-T is Benign according to our data. Variant chr12-10847181-C-T is described in ClinVar as [Benign]. Clinvar id is 3060846.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRR4	NM_007244.3 linkuse as main transcript	c.287G>A	p.Arg96Gln	missense_variant	3/4	ENST00000228811.8
PRH1-PRR4	NR_037918.2 linkuse as main transcript	n.1407G>A		non_coding_transcript_exon_variant	9/10
PRR4	NM_001098538.3 linkuse as main transcript	c.101-46G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR4	ENST00000228811.8 linkuse as main transcript	c.287G>A	p.Arg96Gln	missense_variant	3/4	1	NM_007244.3	P1	Q16378-1

Frequencies

GnomAD3 genomes

AF:

0.490

AC:

74200

AN:

151578

Hom.:

20673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.539

Gnomad AMR

AF:

0.608

Gnomad ASJ

AF:

0.672

Gnomad EAS

AF:

0.708

Gnomad SAS

AF:

0.660

Gnomad FIN

AF:

0.627

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.571

Gnomad OTH

AF:

0.533

GnomAD3 exomes

AF:

0.597

AC:

148759

AN:

249200

Hom.:

46033

AF XY:

0.605

AC XY:

81740

AN XY:

135182

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.647

Gnomad ASJ exome

AF:

0.669

Gnomad EAS exome

AF:

0.716

Gnomad SAS exome

AF:

0.679

Gnomad FIN exome

AF:

0.623

Gnomad NFE exome

AF:

0.583

Gnomad OTH exome

AF:

0.610

GnomAD4 exome

AF:

0.578

AC:

844212

AN:

1461072

Hom.:

247888

Cov.:

AF XY:

0.582

AC XY:

422903

AN XY:

726814

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.646

Gnomad4 ASJ exome

AF:

0.670

Gnomad4 EAS exome

AF:

0.729

Gnomad4 SAS exome

AF:

0.670

Gnomad4 FIN exome

AF:

0.618

Gnomad4 NFE exome

AF:

0.569

Gnomad4 OTH exome

AF:

0.577

GnomAD4 genome

AF:

0.489

AC:

74201

AN:

151696

Hom.:

20668

Cov.:

AF XY:

0.498

AC XY:

36861

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.608

Gnomad4 ASJ

AF:

0.672

Gnomad4 EAS

AF:

0.708

Gnomad4 SAS

AF:

0.660

Gnomad4 FIN

AF:

0.627

Gnomad4 NFE

AF:

0.571

Gnomad4 OTH

AF:

0.535

Alfa

AF:

0.572

Hom.:

47032

Bravo

AF:

0.475

TwinsUK

AF:

0.565

AC:

2095

ALSPAC

AF:

0.567

AC:

2184

ESP6500AA

AF:

0.210

AC:

850

ESP6500EA

AF:

0.579

AC:

4834

ExAC

AF:

0.589

AC:

71210

Asia WGS

AF:

0.642

AC:

2232

AN:

3478

EpiCase

AF:

0.589

EpiControl

AF:

0.589

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PRR4-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.90

BayesDel_noAF

Benign

-0.92

Cadd

Benign

0.050

Dann

Benign

0.85

DEOGEN2

Benign

0.0023

T;T

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.00069

MetaRNN

Benign

0.0000023

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.75

N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.25

PROVEAN

Benign

1.4

N;.

REVEL

Benign

0.013

Sift

Benign

0.83

T;.

Sift4G

Benign

0.89

T;T

Polyphen

0.0060

B;.

Vest4

0.045

MPC

0.090

ClinPred

0.0076

GERP RS

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.015

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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