Variant 11-36462576-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001160167.2(PRR5L):c.947C>A(p.Ala316Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000602 in 1,612,876 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00063 ( 0 hom. )

Consequence

PRR5L
NM_001160167.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.07

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027291745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRR5L	NM_001160167.2 linkuse as main transcript	c.947C>A	p.Ala316Asp	missense_variant	9/9	ENST00000530639.6
PRR5L	NM_024841.5 linkuse as main transcript	c.947C>A	p.Ala316Asp	missense_variant	10/10
PRR5L	NM_001160168.2 linkuse as main transcript	c.563C>A	p.Ala188Asp	missense_variant	6/6
PRR5L	NM_001160169.1 linkuse as main transcript	c.*202C>A		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR5L	ENST00000530639.6 linkuse as main transcript	c.947C>A	p.Ala316Asp	missense_variant	9/9	2	NM_001160167.2	P1	Q6MZQ0-1

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000327

AC:

AN:

247566

Hom.:

AF XY:

0.000313

AC XY:

AN XY:

134276

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.000174

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:

0.000642

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000631

AC:

921

AN:

1460694

Hom.:

Cov.:

AF XY:

0.000572

AC XY:

416

AN XY:

726650

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000800

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000329

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000444

Hom.:

Bravo

AF:

0.000317

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000830

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

Nov 08, 2022

The c.947C>A (p.A316D) alteration is located in exon 9 (coding exon 8) of the PRR5L gene. This alteration results from a C to A substitution at nucleotide position 947, causing the alanine (A) at amino acid position 316 to be replaced by an aspartic acid (D). 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

0.086

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.39

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.0030

T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.43

M_CAP

Benign

0.038

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.19

Sift

Benign

0.090

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0

B;B

Vest4

0.13

MVP

0.40

MPC

0.41

ClinPred

0.020

GERP RS

4.3

Varity_R

0.20

gMVP

0.40

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