12-10847109-T-C

Position:

chr12-10847109-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_007244.3(PRR4):c.359A>G(p.Gln120Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 1,609,774 control chromosomes in the GnomAD database, including 541,748 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.72 ( 42612 hom., cov: 31)

Exomes 𝑓: 0.82 ( 499136 hom. )

Consequence

PRR4
NM_007244.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.61

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2321364E-6).

BP6

Variant 12-10847109-T-C is Benign according to our data. Variant chr12-10847109-T-C is described in ClinVar as [Benign]. Clinvar id is 3060347.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRR4	NM_007244.3 linkuse as main transcript	c.359A>G	p.Gln120Arg	missense_variant	3/4	ENST00000228811.8
PRH1-PRR4	NR_037918.2 linkuse as main transcript	n.1479A>G		non_coding_transcript_exon_variant	9/10
PRR4	NM_001098538.3 linkuse as main transcript	c.127A>G	p.Arg43Gly	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR4	ENST00000228811.8 linkuse as main transcript	c.359A>G	p.Gln120Arg	missense_variant	3/4	1	NM_007244.3	P1	Q16378-1

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110161

AN:

151914

Hom.:

42604

Cov.:

show subpopulations

Gnomad AFR

AF:

0.428

Gnomad AMI

AF:

0.590

Gnomad AMR

AF:

0.830

Gnomad ASJ

AF:

0.850

Gnomad EAS

AF:

0.931

Gnomad SAS

AF:

0.842

Gnomad FIN

AF:

0.890

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.827

Gnomad OTH

AF:

0.757

GnomAD3 exomes

AF:

0.830

AC:

205465

AN:

247600

Hom.:

86727

AF XY:

0.835

AC XY:

112026

AN XY:

134228

show subpopulations

Gnomad AFR exome

AF:

0.426

Gnomad AMR exome

AF:

0.883

Gnomad ASJ exome

AF:

0.845

Gnomad EAS exome

AF:

0.933

Gnomad SAS exome

AF:

0.857

Gnomad FIN exome

AF:

0.888

Gnomad NFE exome

AF:

0.833

Gnomad OTH exome

AF:

0.837

GnomAD4 exome

AF:

0.824

AC:

1201796

AN:

1457740

Hom.:

499136

Cov.:

AF XY:

0.826

AC XY:

598968

AN XY:

724946

show subpopulations

Gnomad4 AFR exome

AF:

0.423

Gnomad4 AMR exome

AF:

0.879

Gnomad4 ASJ exome

AF:

0.846

Gnomad4 EAS exome

AF:

0.945

Gnomad4 SAS exome

AF:

0.848

Gnomad4 FIN exome

AF:

0.887

Gnomad4 NFE exome

AF:

0.825

Gnomad4 OTH exome

AF:

0.817

GnomAD4 genome

AF:

0.725

AC:

110183

AN:

152034

Hom.:

42612

Cov.:

AF XY:

0.733

AC XY:

54469

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.427

Gnomad4 AMR

AF:

0.831

Gnomad4 ASJ

AF:

0.850

Gnomad4 EAS

AF:

0.930

Gnomad4 SAS

AF:

0.842

Gnomad4 FIN

AF:

0.890

Gnomad4 NFE

AF:

0.827

Gnomad4 OTH

AF:

0.758

Alfa

AF:

0.815

Hom.:

113215

Bravo

AF:

0.706

TwinsUK

AF:

0.818

AC:

3033

ALSPAC

AF:

0.828

AC:

3193

ESP6500AA

AF:

0.465

AC:

1840

ESP6500EA

AF:

0.828

AC:

6918

ExAC

AF:

0.821

AC:

99243

Asia WGS

AF:

0.871

AC:

3029

AN:

3478

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

0.064

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.046

DANN

Benign

0.21

DEOGEN2

Benign

0.020

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0036

MetaRNN

Benign

0.0000012

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.0

REVEL

Benign

0.047

Sift

Benign

0.73

Sift4G

Benign

0.23

Polyphen

0.69

Vest4

0.024

MPC

0.047

ClinPred

0.011

GERP RS

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.070

gMVP

0.017

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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