11-36462565-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001160167.2(PRR5L):c.936G>T(p.Leu312=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,612,760 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (47 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (35 hom.)
• Consequence: PRR5L NM_001160167.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0410

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 11-36462565-G-T is Benign according to our data. Variant chr11-36462565-G-T is described in ClinVar as [Benign]. Clinvar id is 790088.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.041 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (2042/152288) while in subpopulation AFR AF= 0.0463 (1926/41564). AF 95% confidence interval is 0.0446. There are 47 homozygotes in gnomad4. There are 954 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRR5L	NM_001160167.2	c.936G>T	p.Leu312=	synonymous_variant	9/9	ENST00000530639.6
PRR5L	NM_024841.5	c.936G>T	p.Leu312=	synonymous_variant	10/10
PRR5L	NM_001160168.2	c.552G>T	p.Leu184=	synonymous_variant	6/6
PRR5L	NM_001160169.1	c.*191G>T		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR5L	ENST00000530639.6	c.936G>T	p.Leu312=	synonymous_variant	9/9	2	NM_001160167.2	P1

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2031 AN: 152170 Hom.: 47 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.00340 AC: 840 AN: 247064 Hom.: 14 AF XY: 0.00228 AC XY: 306 AN XY: 133982

Gnomad AFR exome AF: 0.0475

Gnomad AMR exome AF: 0.00203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000544

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.00125 AC: 1819 AN: 1460472 Hom.: 35 Cov.: 30 AF XY: 0.00107 AC XY: 774 AN XY: 726508

Gnomad4 AFR exome AF: 0.0447

Gnomad4 AMR exome AF: 0.00253

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000813

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000225

Gnomad4 OTH exome AF: 0.00278

GnomAD4 genome AF: 0.0134 AC: 2042 AN: 152288 Hom.: 47 Cov.: 32 AF XY: 0.0128 AC XY: 954 AN XY: 74456

Gnomad4 AFR AF: 0.0463

Gnomad4 AMR AF: 0.00529

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00493 Hom.: 7

Bravo AF: 0.0148

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	0.035
Dann	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs34680620; hg19: chr11-36484115;