Genetic Variant PRR4:p.Gln120Pro (chr12-10847109-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007244.3(PRR4):c.359A>C(p.Gln120Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q120R) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PRR4
NM_007244.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.61

Publications

0 publications found

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:

ENSG00000275778 (HGNC:):

ENSG00000275778 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08041665).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007244.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PRR4	NM_007244.3	MANE Select	c.359A>C	p.Gln120Pro	missense	Exon 3 of 4	NP_009175.2
PRR4	NM_001098538.3		c.127A>C	p.Arg43Arg	synonymous	Exon 3 of 4	NP_001092008.2
PRH1-PRR4	NR_037918.2		n.1479A>C		non_coding_transcript_exon	Exon 9 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PRR4	ENST00000228811.8	TSL:1 MANE Select	c.359A>C	p.Gln120Pro	missense	Exon 3 of 4	ENSP00000228811.4
PRR4	ENST00000544994.5	TSL:1	c.127A>C	p.Arg43Arg	synonymous	Exon 3 of 4	ENSP00000438046.1
ENSG00000275778	ENST00000536668.2	TSL:5	n.*313A>C		non_coding_transcript_exon	Exon 9 of 10	ENSP00000482961.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725164

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44558

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26000

East Asian (EAS)

AF:

0.00

AC:

AN:

39638

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85500

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109786

Other (OTH)

AF:

0.00

AC:

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.040

(source)

DANN

Benign

0.22

DEOGEN2

Benign

0.011

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0054

M_CAP

Benign

0.0033

MetaRNN

Benign

0.080

MetaSVM

Benign

-1.1

PhyloP100

-2.6

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.6

REVEL

Benign

0.11

Sift

Benign

0.044

Sift4G

Uncertain

0.020

Polyphen

0.87

Vest4

0.092

MutPred

0.10

Gain of loop (P = 0.0435)

MVP

0.030

MPC

0.069

ClinPred

0.15

GERP RS

-1.5

Varity_R

0.19

gMVP

0.030

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over