12-70746080-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002849.4(PTPRR):c.745T>C(p.Tyr249His) variant causes a missense change. The variant allele was found at a frequency of 0.00137 in 1,610,622 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0013 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (43 hom.)
• Consequence: PTPRR NM_002849.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.15

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007886469).
• BP6: Variant 12-70746080-A-G is Benign according to our data. Variant chr12-70746080-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2643178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRR	NM_002849.4	c.745T>C	p.Tyr249His	missense_variant	6/14	ENST00000283228.7
LOC124902960	XR_007063361.1	n.628+26257A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRR	ENST00000283228.7	c.745T>C	p.Tyr249His	missense_variant	6/14	1	NM_002849.4	P3

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 200 AN: 152160 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.0459

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00257 AC: 636 AN: 247304 Hom.: 13 AF XY: 0.00253 AC XY: 339 AN XY: 133778

Gnomad AFR exome AF: 0.0000620

Gnomad AMR exome AF: 0.000759

Gnomad ASJ exome AF: 0.0529

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000330

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000541

Gnomad OTH exome AF: 0.00331

GnomAD4 exome AF: 0.00138 AC: 2012 AN: 1458462 Hom.: 43 Cov.: 33 AF XY: 0.00143 AC XY: 1037 AN XY: 725614

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.000630

Gnomad4 ASJ exome AF: 0.0535

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000304

Gnomad4 OTH exome AF: 0.00407

GnomAD4 genome AF: 0.00131 AC: 200 AN: 152160 Hom.: 2 Cov.: 32 AF XY: 0.00125 AC XY: 93 AN XY: 74332

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.0459

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000367

Gnomad4 OTH AF: 0.00144

Alfa AF: 0.00269 Hom.: 11

Bravo AF: 0.00162

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00291 AC: 25

ExAC AF: 0.00175 AC: 212

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

PTPRR: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.28
Cadd	Uncertain	25
Dann	Uncertain	0.99
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.0079	T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	0.95	D;D;D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.18	N;N;N;N;N;N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;T;D;D;D;D
Sift4G	Benign	0.11	T;T;T;T;T;.
Polyphen		1.0, 1.0	.;D;D;.;.;.
Vest4		0.82
MVP		0.56
MPC		0.63
ClinPred		0.11	T
GERP RS		2.9
Varity_R		0.091
gMVP		0.73

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: rs35987017; hg19: chr12-71139860;