11-36462395-C-T

Position:

• chr11-36462395-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001160167.2(PRR5L):​c.766C>T​(p.Pro256Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRR5L NM_001160167.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58

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 (HGNC:):

ACMG classification

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=0.07917437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR5L	NM_001160167.2	c.766C>T	p.Pro256Ser	missense_variant	9/9	ENST00000530639.6	NP_001153639.1
PRR5L	NM_024841.5	c.766C>T	p.Pro256Ser	missense_variant	10/10		NP_079117.3
PRR5L	NM_001160168.2	c.382C>T	p.Pro128Ser	missense_variant	6/6		NP_001153640.1
PRR5L	NM_001160169.1	c.*21C>T		3_prime_UTR_variant	7/7		NP_001153641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR5L	ENST00000530639.6	c.766C>T	p.Pro256Ser	missense_variant	9/9	2	NM_001160167.2	ENSP00000435050.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2023

The c.766C>T (p.P256S) alteration is located in exon 9 (coding exon 8) of the PRR5L gene. This alteration results from a C to T substitution at nucleotide position 766, causing the proline (P) at amino acid position 256 to be replaced by a serine (S). 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	0.074
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.8
DANN	Benign	0.82
DEOGEN2	Benign	0.025	T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.67	.;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.13
Sift	Benign	0.10	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.025	B;B
Vest4		0.035
MutPred		0.49		Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);
MVP		0.40
MPC		0.29
ClinPred		0.075	T
GERP RS		0.73
Varity_R		0.029
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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.

Other links and lift over

hg19: chr11-36483945; COSMIC: COSV100286980;