Variant 11-18744101-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000358540.7(PTPN5):c.196T>C(p.Ser66Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,611,294 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.0088 ( 11 hom., cov: 32)

Exomes 𝑓: 0.012 ( 156 hom. )

Consequence

PTPN5
ENST00000358540.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.854

Variant links:

Genes affected

PTPN5 (HGNC:9657): (protein tyrosine phosphatase non-receptor type 5) Enables phosphotyrosine residue binding activity. Predicted to be involved in peptidyl-tyrosine dephosphorylation. Predicted to act upstream of or within protein dephosphorylation. Predicted to be located in nucleoplasm. Predicted to be integral component of membrane. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

PTPN5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043842196).

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN5	NM_006906.2 linkuse as main transcript	c.196T>C	p.Ser66Pro	missense_variant	4/15	ENST00000358540.7	NP_008837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN5	ENST00000358540.7 linkuse as main transcript	c.196T>C	p.Ser66Pro	missense_variant	4/15	1	NM_006906.2	ENSP00000351342		P54829-1
PTPN5	ENST00000396168.1 linkuse as main transcript	c.124T>C	p.Ser42Pro	missense_variant	3/14	1		ENSP00000379471	P1	P54829-3
PTPN5	ENST00000396170.5 linkuse as main transcript	c.196T>C	p.Ser66Pro	missense_variant	4/15	2		ENSP00000379473		P54829-2
PTPN5	ENST00000496201.2 linkuse as main transcript	n.243T>C		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes

AF:

0.00882

AC:

1341

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.0297

Gnomad AMR

AF:

0.00615

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00250

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0142

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00778

AC:

1920

AN:

246726

Hom.:

AF XY:

0.00802

AC XY:

1073

AN XY:

133712

show subpopulations

Gnomad AFR exome

AF:

0.00199

Gnomad AMR exome

AF:

0.00243

Gnomad ASJ exome

AF:

0.00140

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00273

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.00628

GnomAD4 exome

AF:

0.0124

AC:

18165

AN:

1459072

Hom.:

156

Cov.:

AF XY:

0.0121

AC XY:

8798

AN XY:

725928

show subpopulations

Gnomad4 AFR exome

AF:

0.00180

Gnomad4 AMR exome

AF:

0.00265

Gnomad4 ASJ exome

AF:

0.00207

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00262

Gnomad4 FIN exome

AF:

0.0112

Gnomad4 NFE exome

AF:

0.0149

Gnomad4 OTH exome

AF:

0.00961

GnomAD4 genome

AF:

0.00879

AC:

1338

AN:

152222

Hom.:

Cov.:

AF XY:

0.00848

AC XY:

631

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00229

Gnomad4 AMR

AF:

0.00614

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00229

Gnomad4 FIN

AF:

0.0116

Gnomad4 NFE

AF:

0.0142

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.0121

Hom.:

Bravo

AF:

0.00804

TwinsUK

AF:

0.0189

AC:

ALSPAC

AF:

0.0163

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0129

AC:

111

ExAC

AF:

0.00727

AC:

883

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.063

T;.;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.60

T;T;T

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

N;N;.

MutationTaster

Benign

0.98

N;N;N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.074

Sift

Benign

0.28

T;T;T

Sift4G

Benign

0.082

T;D;T

Polyphen

0.0010

B;.;.

Vest4

0.33

MVP

0.32

MPC

0.37

ClinPred

0.012

GERP RS

-0.96

Varity_R

0.073

gMVP

0.36

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

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