Variant chr11-36462488-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001160167.2(PRR5L):c.859G>C(p.Val287Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PRR5L
NM_001160167.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18162954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR5L	NM_001160167.2 linkuse as main transcript	c.859G>C	p.Val287Leu	missense_variant	9/9	ENST00000530639.6	NP_001153639.1	Q6MZQ0-1B3KNU3
PRR5L	NM_024841.5 linkuse as main transcript	c.859G>C	p.Val287Leu	missense_variant	10/10		NP_079117.3	Q6MZQ0-1
PRR5L	NM_001160168.2 linkuse as main transcript	c.475G>C	p.Val159Leu	missense_variant	6/6		NP_001153640.1	Q6MZQ0-3
PRR5L	NM_001160169.1 linkuse as main transcript	c.*114G>C		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.859G>C	p.Val287Leu	missense_variant	9/9	2	NM_001160167.2	ENSP00000435050.1		Q6MZQ0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456492

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724068

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:

0.0000189

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 04, 2024

The c.859G>C (p.V287L) alteration is located in exon 9 (coding exon 8) of the PRR5L gene. This alteration results from a G to C substitution at nucleotide position 859, causing the valine (V) at amino acid position 287 to be replaced by a leucine (L). 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

0.15

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0067

T;T

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

.;D

M_CAP

Benign

0.074

MetaRNN

Benign

0.18

T;T

MetaSVM

Uncertain

-0.042

MutationAssessor

Benign

1.6

L;L

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.78

N;N

REVEL

Uncertain

0.52

Sift

Uncertain

0.012

D;D

Sift4G

Uncertain

0.022

D;D

Polyphen

0.045

B;B

Vest4

0.20

MutPred

0.36

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.68

MPC

0.27

ClinPred

0.87

GERP RS

4.3

Varity_R

0.14

gMVP

0.42

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over