rs3213550

Variant names:

• chr22-44737460-G-A
• rs3213550
• ENST00000495017.5:n.1904G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000495017.5(PRR5):​n.1904G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,055,018 control chromosomes in the GnomAD database, including 7,936 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 (1920 hom., cov: 33)
  • Exomes 𝑓: 0.10 (6016 hom.)
• Consequence: PRR5 ENST00000495017.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 9 publications found

Genes affected

PRR5 (HGNC:31682): (proline rich 5) This gene encodes a protein with a proline-rich domain. This gene is located in a region of chromosome 22 reported to contain a tumor suppressor gene that may be involved in breast and colorectal tumorigenesis. The protein is a component of the mammalian target of rapamycin complex 2 (mTORC2), and it regulates platelet-derived growth factor (PDGF) receptor beta expression and PDGF signaling to Akt and S6K1. Alternative splicing and the use of alternative promoters results in transcripts encoding different isoforms. Read-through transcripts from this gene into the downstream Rho GTPase activating protein 8 (ARHGAP8) gene also exist, which led to the original description of PRR5 and ARHGAP8 being a single gene. [provided by RefSeq, Nov 2010]

PRR5-ARHGAP8 (HGNC:34512): (PRR5-ARHGAP8 readthrough) The PRR5-ARHGAP8 mRNA is an infrequent but naturally occurring read-through transcript of the neighboring proline rich 5, renal (PRR5) and Rho GTPase activating protein 8 (ARHGAP8) genes. The resulting fusion protein contains sequence identity with each individual gene product, and it includes domains characteristic of a RhoGAP protein. The significance of this read-through transcript and the function of its protein product have not yet been determined. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR5	NM_181333.4	c.*213G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000336985.11	NP_851850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR5	ENST00000336985.11	c.*213G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_181333.4	ENSP00000337464.6
PRR5-ARHGAP8	ENST00000352766.11	c.691+2298G>A		intron_variant	Intron 7 of 16	2		ENSP00000262731.11

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21439 AN: 152026 Hom.: 1914 Cov.: 33

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.0907

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0951

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0949

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.103 AC: 93320 AN: 902872 Hom.: 6016 Cov.: 12 AF XY: 0.103 AC XY: 45477 AN XY: 442788

African (AFR) AF: 0.246 AC: 5196 AN: 21150

American (AMR) AF: 0.0734 AC: 1257 AN: 17136

Ashkenazi Jewish (ASJ) AF: 0.0905 AC: 1408 AN: 15558

East Asian (EAS) AF: 0.296 AC: 9302 AN: 31390

South Asian (SAS) AF: 0.0983 AC: 4270 AN: 43424

European-Finnish (FIN) AF: 0.0917 AC: 2426 AN: 26448

Middle Eastern (MID) AF: 0.119 AC: 331 AN: 2776

European-Non Finnish (NFE) AF: 0.0916 AC: 64578 AN: 705284

Other (OTH) AF: 0.115 AC: 4552 AN: 39706

GnomAD4 genome AF: 0.141 AC: 21458 AN: 152146 Hom.: 1920 Cov.: 33 AF XY: 0.141 AC XY: 10494 AN XY: 74392

African (AFR) AF: 0.240 AC: 9940 AN: 41500

American (AMR) AF: 0.0906 AC: 1386 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0899 AC: 312 AN: 3472

East Asian (EAS) AF: 0.269 AC: 1386 AN: 5150

South Asian (SAS) AF: 0.101 AC: 486 AN: 4826

European-Finnish (FIN) AF: 0.0951 AC: 1009 AN: 10610

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0948 AC: 6446 AN: 67972

Other (OTH) AF: 0.132 AC: 279 AN: 2112

Alfa AF: 0.104 Hom.: 1503

Bravo AF: 0.147

Asia WGS AF: 0.199 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.60
DANN	Benign	0.64
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs3213550; hg19: chr22-45133340;