Variant chr11-36462413-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001160167.2(PRR5L):c.784C>T(p.Arg262Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000045 in 1,577,170 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

PRR5L
NM_001160167.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.20

Variant links:

Genes affected

PRR5L (HGNC:25878): (proline rich 5 like) Enables ubiquitin protein ligase binding activity. Involved in several processes, including TORC2 signaling; positive regulation of mRNA catabolic process; and regulation of fibroblast migration. Part of TORC2 complex. [provided by Alliance of Genome Resources, Apr 2022]

PRR5L links:

PRR5L (HGNC:):

PRR5L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR5L	NM_001160167.2 linkuse as main transcript	c.784C>T	p.Arg262Trp	missense_variant	9/9	ENST00000530639.6	NP_001153639.1	Q6MZQ0-1B3KNU3
PRR5L	NM_024841.5 linkuse as main transcript	c.784C>T	p.Arg262Trp	missense_variant	10/10		NP_079117.3	Q6MZQ0-1
PRR5L	NM_001160168.2 linkuse as main transcript	c.400C>T	p.Arg134Trp	missense_variant	6/6		NP_001153640.1	Q6MZQ0-3
PRR5L	NM_001160169.1 linkuse as main transcript	c.*39C>T		3_prime_UTR_variant	7/7		NP_001153641.1	Q6MZQ0-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR5L	ENST00000530639.6 linkuse as main transcript	c.784C>T	p.Arg262Trp	missense_variant	9/9	2	NM_001160167.2	ENSP00000435050.1		Q6MZQ0-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000493

AC:

AN:

223332

Hom.:

AF XY:

0.0000335

AC XY:

AN XY:

119540

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000400

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000897

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000470

AC:

AN:

1424840

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

704000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000846

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000248

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000568

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000979

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

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 28, 2023

The c.784C>T (p.R262W) alteration is located in exon 9 (coding exon 8) of the PRR5L gene. This alteration results from a C to T substitution at nucleotide position 784, causing the arginine (R) at amino acid position 262 to be replaced by a tryptophan (W). 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

Benign

0.096

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.079

T;T

Eigen

Pathogenic

0.68

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

.;D

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Uncertain

0.55

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.2

D;D

REVEL

Uncertain

0.60

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;D

Vest4

0.49

MVP

0.69

MPC

0.64

ClinPred

0.67

GERP RS

5.3

Varity_R

0.24

gMVP

0.47

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