rs73341069

Positions:

• chr12-70754214-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000283228.7(PTPRR):​c.715G>A​(p.Val239Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,613,444 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (39 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (36 hom.)
• Consequence: PTPRR ENST00000283228.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

Genes affected

PTPRR (HGNC:9680): (protein tyrosine phosphatase receptor type R) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and a single intracellular catalytic domain, and thus represents a receptor-type PTP. Silencing of this gene has been associated with colorectal cancer. Multiple transcript variants encoding different isoforms have been found for this gene. This gene shares a symbol (PTPRQ) with another gene, protein tyrosine phosphatase, receptor type, Q (GeneID 374462), which is also located on chromosome 12. [provided by RefSeq, May 2011]

LOC124902960 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030323863).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1782/152232) while in subpopulation AFR AF= 0.0406 (1687/41524). AF 95% confidence interval is 0.039. There are 39 homozygotes in gnomad4. There are 838 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRR	NM_002849.4	c.715G>A	p.Val239Ile	missense_variant	5/14	ENST00000283228.7	NP_002840.2
LOC124902960	XR_007063361.1	n.629-19223C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRR	ENST00000283228.7	c.715G>A	p.Val239Ile	missense_variant	5/14	1	NM_002849.4	ENSP00000283228	P3

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1772 AN: 152114 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00329 AC: 822 AN: 250046 Hom.: 17 AF XY: 0.00268 AC XY: 362 AN XY: 135166

Gnomad AFR exome AF: 0.0429

Gnomad AMR exome AF: 0.00273

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000177

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00125 AC: 1827 AN: 1461212 Hom.: 36 Cov.: 31 AF XY: 0.00113 AC XY: 821 AN XY: 726880

Gnomad4 AFR exome AF: 0.0400

Gnomad4 AMR exome AF: 0.00300

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000980

Gnomad4 OTH exome AF: 0.00355

GnomAD4 genome AF: 0.0117 AC: 1782 AN: 152232 Hom.: 39 Cov.: 32 AF XY: 0.0113 AC XY: 838 AN XY: 74414

Gnomad4 AFR AF: 0.0406

Gnomad4 AMR AF: 0.00406

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00186 Hom.: 7

Bravo AF: 0.0133

ESP6500AA AF: 0.0381 AC: 168

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00409 AC: 497

Asia WGS AF: 0.00289 AC: 11 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.11	.;T;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.76	T;T;T
MetaRNN	Benign	0.0030	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.77	.;N;.
MutationTaster	Benign	1.0	D;D;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.020	N;N;N
REVEL	Benign	0.062
Sift	Benign	0.50	T;T;T
Sift4G	Benign	0.64	T;T;T
Polyphen		0.0020	B;B;.
Vest4		0.21
MVP		0.46
MPC		0.092
ClinPred		0.0075	T
GERP RS		0.29
Varity_R		0.036
gMVP		0.33

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: rs73341069; hg19: chr12-71147994;