Variant 12-70596274-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000334414.11(PTPRB):c.1033A>G(p.Ser345Gly) variant causes a missense change. The variant allele was found at a frequency of 0.283 in 1,610,220 control chromosomes in the GnomAD database, including 66,100 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 0.31 ( 7493 hom., cov: 28)

Exomes 𝑓: 0.28 ( 58607 hom. )

Consequence

PTPRB
ENST00000334414.11 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.00

Variant links:

Genes affected

PTPRB (HGNC:9665): (protein tyrosine phosphatase receptor type B) 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 contains an extracellular domain, a single transmembrane segment and one intracytoplasmic catalytic domain, thus belongs to receptor type PTP. The extracellular region of this PTP is composed of multiple fibronectin type_III repeats, which was shown to interact with neuronal receptor and cell adhesion molecules, such as contactin and tenascin C. This protein was also found to interact with sodium channels, and thus may regulate sodium channels by altering tyrosine phosphorylation status. The functions of the interaction partners of this protein implicate the roles of this PTP in cell adhesion, neurite growth, and neuronal differentiation. Alternate transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

PTPRB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005496502).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRB	NM_001109754.4 linkuse as main transcript	c.1033A>G	p.Ser345Gly	missense_variant	5/34	ENST00000334414.11	NP_001103224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRB	ENST00000334414.11 linkuse as main transcript	c.1033A>G	p.Ser345Gly	missense_variant	5/34	1	NM_001109754.4	ENSP00000334928	A1	P23467-3

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46315

AN:

150446

Hom.:

7479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.314

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.313

GnomAD3 exomes

AF:

0.267

AC:

65929

AN:

246676

Hom.:

9137

AF XY:

0.268

AC XY:

35934

AN XY:

133894

show subpopulations

Gnomad AFR exome

AF:

0.422

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.296

Gnomad SAS exome

AF:

0.261

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.274

Gnomad OTH exome

AF:

0.270

GnomAD4 exome

AF:

0.281

AC:

410063

AN:

1459662

Hom.:

58607

Cov.:

AF XY:

0.280

AC XY:

203250

AN XY:

725934

show subpopulations

Gnomad4 AFR exome

AF:

0.420

Gnomad4 AMR exome

AF:

0.199

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.309

Gnomad4 SAS exome

AF:

0.267

Gnomad4 FIN exome

AF:

0.236

Gnomad4 NFE exome

AF:

0.283

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.308

AC:

46365

AN:

150558

Hom.:

7493

Cov.:

AF XY:

0.305

AC XY:

22366

AN XY:

73416

show subpopulations

Gnomad4 AFR

AF:

0.416

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.244

Gnomad4 EAS

AF:

0.314

Gnomad4 SAS

AF:

0.283

Gnomad4 FIN

AF:

0.232

Gnomad4 NFE

AF:

0.276

Gnomad4 OTH

AF:

0.313

Alfa

AF:

0.279

Hom.:

12589

Bravo

AF:

0.313

TwinsUK

AF:

0.285

AC:

1055

ALSPAC

AF:

0.287

AC:

1108

ESP6500AA

AF:

0.397

AC:

1481

ESP6500EA

AF:

0.278

AC:

2290

ExAC

AF:

0.272

AC:

32791

Asia WGS

AF:

0.279

AC:

974

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

.;T;.;.;T;T;T

Eigen

Benign

-0.037

Eigen_PC

Benign

0.056

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.70

T;T;T;T;T;T;T

MetaRNN

Benign

0.0055

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

.;.;M;M;M;.;.

MutationTaster

Benign

0.017

P;P;P;P;P;P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.3

N;N;N;N;N;N;N

REVEL

Benign

0.21

Sift

Uncertain

0.014

D;D;D;T;T;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D;D;D

Polyphen

0.0070

B;B;.;B;B;B;B

Vest4

0.66

MPC

0.10

ClinPred

0.039

GERP RS

5.8

Varity_R

0.25

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over