11-36437447-A-G

Position:

• chr11-36437447-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001160167.2(PRR5L):​c.415A>G​(p.Thr139Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0404 in 1,609,680 control chromosomes in the GnomAD database, including 1,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (130 hom., cov: 32)
  • Exomes 𝑓: 0.041 (1579 hom.)
• Consequence: PRR5L NM_001160167.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.62

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003241539).
• BP6: Variant 11-36437447-A-G is Benign according to our data. Variant chr11-36437447-A-G is described in ClinVar as [Benign]. Clinvar id is 1227648.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0341 (5189/152068) while in subpopulation NFE AF= 0.0426 (2894/67990). AF 95% confidence interval is 0.0413. There are 130 homozygotes in gnomad4. There are 2659 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 130 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRR5L	NM_001160167.2	c.415A>G	p.Thr139Ala	missense_variant	6/9	ENST00000530639.6
PRR5L	NM_024841.5	c.415A>G	p.Thr139Ala	missense_variant	7/10
PRR5L	NM_001160168.2	c.172A>G	p.Thr58Ala	missense_variant	4/6
PRR5L	NM_001160169.1	c.415A>G	p.Thr139Ala	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR5L	ENST00000530639.6	c.415A>G	p.Thr139Ala	missense_variant	6/9	2	NM_001160167.2	P1
PRR5L	ENST00000378867.7	c.415A>G	p.Thr139Ala	missense_variant	7/10	1		P1
PRR5L	ENST00000527487.1	c.415A>G	p.Thr139Ala	missense_variant	5/7	3
PRR5L	ENST00000389693.3	n.291A>G		non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes AF: 0.0342 AC: 5196 AN: 151950 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.00728

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0271

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0222

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0426

Gnomad OTH AF: 0.0325

GnomAD3 exomes AF: 0.0391 AC: 9799 AN: 250592 Hom.: 311 AF XY: 0.0399 AC XY: 5398 AN XY: 135430

Gnomad AFR exome AF: 0.00665

Gnomad AMR exome AF: 0.0160

Gnomad ASJ exome AF: 0.0372

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0227

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.0462

Gnomad OTH exome AF: 0.0457

GnomAD4 exome AF: 0.0411 AC: 59879 AN: 1457612 Hom.: 1579 Cov.: 29 AF XY: 0.0406 AC XY: 29483 AN XY: 725414

Gnomad4 AFR exome AF: 0.00623

Gnomad4 AMR exome AF: 0.0167

Gnomad4 ASJ exome AF: 0.0363

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0230

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.0427

Gnomad4 OTH exome AF: 0.0387

GnomAD4 genome AF: 0.0341 AC: 5189 AN: 152068 Hom.: 130 Cov.: 32 AF XY: 0.0358 AC XY: 2659 AN XY: 74314

Gnomad4 AFR AF: 0.00726

Gnomad4 AMR AF: 0.0269

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.0426

Gnomad4 OTH AF: 0.0313

Alfa AF: 0.0391 Hom.: 228

Bravo AF: 0.0260

TwinsUK AF: 0.0429 AC: 159

ALSPAC AF: 0.0420 AC: 162

ESP6500AA AF: 0.00568 AC: 25

ESP6500EA AF: 0.0407 AC: 350

ExAC AF: 0.0391 AC: 4741

Asia WGS AF: 0.0110 AC: 37 AN: 3478

EpiCase AF: 0.0412

EpiControl AF: 0.0418

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

GeneDx

Apr 19, 2019

This variant is associated with the following publications: (PMID: 30389748) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T;T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
MetaRNN	Benign	0.0032	T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.9	M;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.18
Sift	Benign	0.11	T;T;T
Sift4G	Uncertain	0.031	D;D;T
Polyphen		0.73	P;P;.
Vest4		0.24
MPC		0.83
ClinPred		0.037	T
GERP RS		5.3
Varity_R		0.23
gMVP		0.40

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: rs62621409; hg19: chr11-36458997;