chr1-43569746-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002840.5(PTPRF):c.536C>T(p.Thr179Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,612,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

PTPRF
NM_002840.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Publications

3 publications found

Variant links:

Genes affected

PTPRF (HGNC:9670): (protein tyrosine phosphatase receptor type F) 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 two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains three Ig-like domains, and nine non-Ig like domains similar to that of neural-cell adhesion molecule. This PTP was shown to function in the regulation of epithelial cell-cell contacts at adherents junctions, as well as in the control of beta-catenin signaling. An increased expression level of this protein was found in the insulin-responsive tissue of obese, insulin-resistant individuals, and may contribute to the pathogenesis of insulin resistance. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

PTPRF Gene-Disease associations (from GenCC):

breasts and/or nipples, aplasia or hypoplasia of, 2
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

PTPRF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12601048).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002840.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPRF	NM_002840.5	MANE Select	c.536C>T	p.Thr179Met	missense	Exon 6 of 34	NP_002831.2	P10586-1
PTPRF	NM_130440.4		c.536C>T	p.Thr179Met	missense	Exon 6 of 33	NP_569707.2	P10586-2
PTPRF	NM_001329138.2		c.536C>T	p.Thr179Met	missense	Exon 7 of 37	NP_001316067.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPRF	ENST00000359947.9	TSL:1 MANE Select	c.536C>T	p.Thr179Met	missense	Exon 6 of 34	ENSP00000353030.4	P10586-1
PTPRF	ENST00000438120.5	TSL:1	c.536C>T	p.Thr179Met	missense	Exon 6 of 33	ENSP00000398822.1	P10586-2
PTPRF	ENST00000437607.1	TSL:1	c.536C>T	p.Thr179Met	missense	Exon 4 of 6	ENSP00000413306.1	A2A437

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000879

AC:

AN:

250284

AF XY:

0.0000887

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000152

AC:

222

AN:

1460676

Hom.:

Cov.:

AF XY:

0.000156

AC XY:

113

AN XY:

726568

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26044

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86146

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.000192

AC:

213

AN:

1111256

Other (OTH)

AF:

0.0000331

AC:

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000118

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41550

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000220

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.81

M_CAP

Benign

0.050

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.4

PhyloP100

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.6

REVEL

Benign

0.086

Sift

Benign

0.16

Sift4G

Uncertain

0.0090

Polyphen

0.98

Vest4

0.22

MVP

0.53

MPC

1.2

ClinPred

0.065

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.051

gMVP

0.23

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over