rs3740958

Variant names:

• chr11-36451250-A-G
• rs3740958
• NM_001160167.2:c.627A>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001160167.2(PRR5L):​c.627A>G​(p.Gln209Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,613,888 control chromosomes in the GnomAD database, including 17,692 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1800 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15892 hom.)
• Consequence: PRR5L NM_001160167.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=1.83 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR5L	NM_001160167.2	c.627A>G	p.Gln209Gln	synonymous_variant	Exon 8 of 9	ENST00000530639.6	NP_001153639.1
PRR5L	NM_024841.5	c.627A>G	p.Gln209Gln	synonymous_variant	Exon 9 of 10		NP_079117.3
PRR5L	NM_001160168.2	c.243A>G	p.Gln81Gln	synonymous_variant	Exon 5 of 6		NP_001153640.1
PRR5L	NM_001160169.1	c.585+4810A>G		intron_variant	Intron 6 of 6		NP_001153641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR5L	ENST00000530639.6	c.627A>G	p.Gln209Gln	synonymous_variant	Exon 8 of 9	2	NM_001160167.2	ENSP00000435050.1
PRR5L	ENST00000378867.7	c.627A>G	p.Gln209Gln	synonymous_variant	Exon 9 of 10	1		ENSP00000368144.3
PRR5L	ENST00000527487.1	c.585+4810A>G		intron_variant	Intron 6 of 6	3		ENSP00000435241.1
PRR5L	ENST00000389693.3	n.362A>G		non_coding_transcript_exon_variant	Exon 5 of 6	2

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21785 AN: 152022 Hom.: 1789 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.0595

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.146

GnomAD3 exomes AF: 0.157 AC: 39474 AN: 251456 Hom.: 3850 AF XY: 0.158 AC XY: 21491 AN XY: 135896

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.390

Gnomad SAS exome AF: 0.214

Gnomad FIN exome AF: 0.0641

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.139 AC: 203861 AN: 1461748 Hom.: 15892 Cov.: 32 AF XY: 0.142 AC XY: 102953 AN XY: 727180

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.335

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.0660

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.144 AC: 21834 AN: 152140 Hom.: 1800 Cov.: 32 AF XY: 0.143 AC XY: 10620 AN XY: 74368

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.0595

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.155

Alfa AF: 0.134 Hom.: 2241

Bravo AF: 0.150

Asia WGS AF: 0.287 AC: 995 AN: 3478

EpiCase AF: 0.126

EpiControl AF: 0.135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.6
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3740958; hg19: chr11-36472800; COSMIC: COSV61121539; COSMIC: COSV61121539;