Variant 11-36451302-G-C 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.679G>C(p.Asp227His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PRR5L
NM_001160167.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.67

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.679G>C	p.Asp227His	missense_variant	8/9	ENST00000530639.6	NP_001153639.1	Q6MZQ0-1B3KNU3
PRR5L	NM_024841.5 linkuse as main transcript	c.679G>C	p.Asp227His	missense_variant	9/10		NP_079117.3	Q6MZQ0-1
PRR5L	NM_001160168.2 linkuse as main transcript	c.295G>C	p.Asp99His	missense_variant	5/6		NP_001153640.1	Q6MZQ0-3
PRR5L	NM_001160169.1 linkuse as main transcript	c.585+4862G>C		intron_variant			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.679G>C	p.Asp227His	missense_variant	8/9	2	NM_001160167.2	ENSP00000435050.1	Q6MZQ0-1
PRR5L	ENST00000378867.7 linkuse as main transcript	c.679G>C	p.Asp227His	missense_variant	9/10	1		ENSP00000368144.3	Q6MZQ0-1
PRR5L	ENST00000527487.1 linkuse as main transcript	c.585+4862G>C		intron_variant		3		ENSP00000435241.1	Q6MZQ0-4
PRR5L	ENST00000389693.3 linkuse as main transcript	n.414G>C		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251464

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

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.:

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

Feb 27, 2023

The c.679G>C (p.D227H) alteration is located in exon 8 (coding exon 7) of the PRR5L gene. This alteration results from a G to C substitution at nucleotide position 679, causing the aspartic acid (D) at amino acid position 227 to be replaced by a histidine (H). 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

0.13

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0053

T;T

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.73

.;T

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.61

D;D

MetaSVM

Uncertain

0.31

MutationAssessor

Benign

2.0

M;M

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.80

N;N

REVEL

Uncertain

0.52

Sift

Benign

0.18

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.99

D;D

Vest4

0.59

MutPred

0.22

Gain of MoRF binding (P = 0.0522);Gain of MoRF binding (P = 0.0522);

MVP

0.63

MPC

1.0

ClinPred

0.73

GERP RS

4.2

Varity_R

0.11

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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