11-36462352-C-T

Variant names:

• chr11-36462352-C-T
• NM_001160167.2:c.723C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.719

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]

ACMG classification

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
PRR5L	NM_001160167.2	c.723C>T	p.His241His	synonymous_variant	Exon 9 of 9	ENST00000530639.6	NP_001153639.1
PRR5L	NM_001160169.1	c.596C>T	p.Thr199Ile	missense_variant	Exon 7 of 7		NP_001153641.1
PRR5L	NM_024841.5	c.723C>T	p.His241His	synonymous_variant	Exon 10 of 10		NP_079117.3
PRR5L	NM_001160168.2	c.339C>T	p.His113His	synonymous_variant	Exon 6 of 6		NP_001153640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR5L	ENST00000530639.6	c.723C>T	p.His241His	synonymous_variant	Exon 9 of 9	2	NM_001160167.2	ENSP00000435050.1

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

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;