11-36462352-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001160169.1(PRR5L):​c.596C>T​(p.Thr199Ile) 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. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PRR5L
NM_001160169.1 missense

Scores

2
13

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.719
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]

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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=0.10266209).
BP6
Variant 11-36462352-C-T is Benign according to our data. Variant chr11-36462352-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3219551.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRR5LNM_001160167.2 linkc.723C>T p.His241His synonymous_variant Exon 9 of 9 ENST00000530639.6 NP_001153639.1 Q6MZQ0-1B3KNU3
PRR5LNM_001160169.1 linkc.596C>T p.Thr199Ile missense_variant Exon 7 of 7 NP_001153641.1 Q6MZQ0-4
PRR5LNM_024841.5 linkc.723C>T p.His241His synonymous_variant Exon 10 of 10 NP_079117.3 Q6MZQ0-1
PRR5LNM_001160168.2 linkc.339C>T p.His113His synonymous_variant Exon 6 of 6 NP_001153640.1 Q6MZQ0-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRR5LENST00000530639.6 linkc.723C>T p.His241His synonymous_variant Exon 9 of 9 2 NM_001160167.2 ENSP00000435050.1 Q6MZQ0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Feb 05, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
9.9
DANN
Uncertain
0.99
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-1.0
T
PROVEAN
Benign
-0.18
N
REVEL
Benign
0.090
Sift
Benign
0.62
T
Sift4G
Uncertain
0.0070
D
Vest4
0.21
MutPred
0.16
Loss of glycosylation at T199 (P = 0.0216);
MVP
0.41
ClinPred
0.080
T
GERP RS
2.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-36483902; API