11-36462352-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 13/18 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -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 VariationId is 3219551.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160169.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR5L	NM_001160167.2	MANE Select	c.723C>T	p.His241His	synonymous	Exon 9 of 9	NP_001153639.1	Q6MZQ0-1
	PRR5L	NM_001160169.1		c.596C>T	p.Thr199Ile	missense	Exon 7 of 7	NP_001153641.1	Q6MZQ0-4
	PRR5L	NM_024841.5		c.723C>T	p.His241His	synonymous	Exon 10 of 10	NP_079117.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR5L	ENST00000530639.6	TSL:2 MANE Select	c.723C>T	p.His241His	synonymous	Exon 9 of 9	ENSP00000435050.1	Q6MZQ0-1
	PRR5L	ENST00000378867.7	TSL:1	c.723C>T	p.His241His	synonymous	Exon 10 of 10	ENSP00000368144.3	Q6MZQ0-1
	PRR5L	ENST00000530627.1	TSL:1	n.169C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
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
PhyloP100		0.72
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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr11-36483902;