Variant 11-36401243-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.122C>A(p.Ala41Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A41T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

PRR5L
NM_001160167.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.17

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=0.062958956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRR5L	NM_001160167.2 linkuse as main transcript	c.122C>A	p.Ala41Asp	missense_variant	2/9	ENST00000530639.6
PRR5L	NM_024841.5 linkuse as main transcript	c.122C>A	p.Ala41Asp	missense_variant	3/10
PRR5L	NM_001160169.1 linkuse as main transcript	c.122C>A	p.Ala41Asp	missense_variant	1/7
PRR5L	NM_001160168.2 linkuse as main transcript	c.3-18012C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR5L	ENST00000530639.6 linkuse as main transcript	c.122C>A	p.Ala41Asp	missense_variant	2/9	2	NM_001160167.2	P1	Q6MZQ0-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000440

AC:

AN:

249962

Hom.:

AF XY:

0.0000591

AC XY:

AN XY:

135370

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.0000308

AC:

AN:

1461048

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000677

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

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 16, 2021

The c.122C>A (p.A41D) alteration is located in exon 2 (coding exon 1) of the PRR5L gene. This alteration results from a C to A substitution at nucleotide position 122, causing the alanine (A) at amino acid position 41 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

0.27

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

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

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.49

M_CAP

Benign

0.016

MetaRNN

Benign

0.063

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

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

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.76

N;D;N;D;N;D;D;D;D;N;N

REVEL

Benign

0.055

Sift

Uncertain

0.0060

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

Sift4G

Uncertain

0.0070

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

Polyphen

0.62

P;.;.;.;P;.;.;.;.;.;.

Vest4

0.29

MutPred

0.28

Loss of MoRF binding (P = 0.0656);Loss of MoRF binding (P = 0.0656);Loss of MoRF binding (P = 0.0656);Loss of MoRF binding (P = 0.0656);Loss of MoRF binding (P = 0.0656);Loss of MoRF binding (P = 0.0656);Loss of MoRF binding (P = 0.0656);Loss of MoRF binding (P = 0.0656);Loss of MoRF binding (P = 0.0656);Loss of MoRF binding (P = 0.0656);Loss of MoRF binding (P = 0.0656);

MVP

0.30

MPC

0.53

ClinPred

0.048

GERP RS

5.2

Varity_R

0.29

gMVP

0.68

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