Variant chr11-36437396-A-G 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.364A>G(p.Ile122Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PRR5L
NM_001160167.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

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=0.13647446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR5L	NM_001160167.2 linkuse as main transcript	c.364A>G	p.Ile122Val	missense_variant	6/9	ENST00000530639.6	NP_001153639.1	Q6MZQ0-1B3KNU3
PRR5L	NM_024841.5 linkuse as main transcript	c.364A>G	p.Ile122Val	missense_variant	7/10		NP_079117.3	Q6MZQ0-1
PRR5L	NM_001160168.2 linkuse as main transcript	c.121A>G	p.Ile41Val	missense_variant	4/6		NP_001153640.1	Q6MZQ0-3
PRR5L	NM_001160169.1 linkuse as main transcript	c.364A>G	p.Ile122Val	missense_variant	5/7		NP_001153641.1	Q6MZQ0-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRR5L	ENST00000530639.6 linkuse as main transcript	c.364A>G	p.Ile122Val	missense_variant	6/9	2	NM_001160167.2	ENSP00000435050.1	Q6MZQ0-1
PRR5L	ENST00000378867.7 linkuse as main transcript	c.364A>G	p.Ile122Val	missense_variant	7/10	1		ENSP00000368144.3	Q6MZQ0-1
PRR5L	ENST00000527487.1 linkuse as main transcript	c.364A>G	p.Ile122Val	missense_variant	5/7	3		ENSP00000435241.1	Q6MZQ0-4
PRR5L	ENST00000389693.3 linkuse as main transcript	n.240A>G		non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251340

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458294

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725836

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000659

Hom.:

ExAC

AF:

0.0000165

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

Jun 28, 2024

The c.364A>G (p.I122V) alteration is located in exon 6 (coding exon 5) of the PRR5L gene. This alteration results from a A to G substitution at nucleotide position 364, causing the isoleucine (I) at amino acid position 122 to be replaced by a valine (V). 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

0.069

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

T;T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.75

.;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.69

N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.80

N;N;N

REVEL

Benign

0.041

Sift

Benign

0.12

T;T;T

Sift4G

Uncertain

0.019

D;D;D

Polyphen

0.010

B;B;.

Vest4

0.20

MutPred

0.61

Gain of methylation at R121 (P = 0.0471);Gain of methylation at R121 (P = 0.0471);Gain of methylation at R121 (P = 0.0471);

MVP

0.40

MPC

0.24

ClinPred

0.22

GERP RS

1.6

Varity_R

0.051

gMVP

0.22

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