Variant chr22-44732384-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_181333.4(PRR5):c.548T>C(p.Val183Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000172 in 1,456,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

PRR5
NM_181333.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.14

Variant links:

Genes affected

PRR5 (HGNC:31682): (proline rich 5) This gene encodes a protein with a proline-rich domain. This gene is located in a region of chromosome 22 reported to contain a tumor suppressor gene that may be involved in breast and colorectal tumorigenesis. The protein is a component of the mammalian target of rapamycin complex 2 (mTORC2), and it regulates platelet-derived growth factor (PDGF) receptor beta expression and PDGF signaling to Akt and S6K1. Alternative splicing and the use of alternative promoters results in transcripts encoding different isoforms. Read-through transcripts from this gene into the downstream Rho GTPase activating protein 8 (ARHGAP8) gene also exist, which led to the original description of PRR5 and ARHGAP8 being a single gene. [provided by RefSeq, Nov 2010]

PRR5 links:

PRR5-ARHGAP8 (HGNC:34512): (PRR5-ARHGAP8 readthrough) The PRR5-ARHGAP8 mRNA is an infrequent but naturally occurring read-through transcript of the neighboring proline rich 5, renal (PRR5) and Rho GTPase activating protein 8 (ARHGAP8) genes. The resulting fusion protein contains sequence identity with each individual gene product, and it includes domains characteristic of a RhoGAP protein. The significance of this read-through transcript and the function of its protein product have not yet been determined. [provided by RefSeq, Nov 2010]

PRR5-ARHGAP8 links:

PRR5 (HGNC:):

PRR5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27713177).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR5	NM_181333.4 linkuse as main transcript	c.548T>C	p.Val183Ala	missense_variant	6/8	ENST00000336985.11	NP_851850.1	P85299-1A8K699

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR5	ENST00000336985.11 linkuse as main transcript	c.548T>C	p.Val183Ala	missense_variant	6/8	1	NM_181333.4	ENSP00000337464.6		P85299-1
PRR5-ARHGAP8	ENST00000352766.11 linkuse as main transcript	c.548T>C	p.Val183Ala	missense_variant	6/17	2		ENSP00000262731.11		B1AHC4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000814

AC:

AN:

245724

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134006

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1456206

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

724298

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

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

Dec 13, 2023

The c.617T>C (p.V206A) alteration is located in exon 8 (coding exon 7) of the PRR5 gene. This alteration results from a T to C substitution at nucleotide position 617, causing the valine (V) at amino acid position 206 to be replaced by an alanine (A). 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

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

.;.;T;.;.;.;T;T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

D;D;D;.;.;D;D;D;D

M_CAP

Benign

0.033

MetaRNN

Benign

0.28

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.6

.;.;.;.;.;.;L;.;.

PROVEAN

Uncertain

-3.2

.;.;D;.;D;D;D;D;N

REVEL

Benign

0.11

Sift

Uncertain

0.0020

.;.;D;.;D;D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D;D;D;D;D

Polyphen

0.83, 0.96

.;.;.;.;.;.;P;.;D

Vest4

0.69

MutPred

0.22

.;.;.;.;.;.;Loss of stability (P = 0.0737);.;Loss of stability (P = 0.0737);

MVP

0.068

MPC

0.31

ClinPred

0.90

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.30

gMVP

0.57

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

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