Variant 11-18740694-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006906.2(PTPN5):c.824G>A(p.Arg275His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,609,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

PTPN5
NM_006906.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.739

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.073491335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN5	NM_006906.2 linkuse as main transcript	c.824G>A	p.Arg275His	missense_variant	8/15	ENST00000358540.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN5	ENST00000358540.7 linkuse as main transcript	c.824G>A	p.Arg275His	missense_variant	8/15	1	NM_006906.2		P54829-1
PTPN5	ENST00000396168.1 linkuse as main transcript	c.752G>A	p.Arg251His	missense_variant	7/14	1		P1	P54829-3
PTPN5	ENST00000396170.5 linkuse as main transcript	c.728G>A	p.Arg243His	missense_variant	8/15	2			P54829-2
PTPN5	ENST00000477854.5 linkuse as main transcript	c.236G>A	p.Arg79His	missense_variant	4/11	5

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

151888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000145

AC:

AN:

248038

Hom.:

AF XY:

0.000127

AC XY:

AN XY:

134104

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000118

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000249

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.000189

AC:

275

AN:

1457198

Hom.:

Cov.:

AF XY:

0.000182

AC XY:

132

AN XY:

724586

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000230

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.000151

AC:

AN:

151888

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000210

Hom.:

Bravo

AF:

0.000174

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000123

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.824G>A (p.R275H) alteration is located in exon 8 (coding exon 7) of the PTPN5 gene. This alteration results from a G to A substitution at nucleotide position 824, causing the arginine (R) at amino acid position 275 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.72

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.77

T;T;T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.073

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.99

N;N;N;N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.040

N;N;N;N

REVEL

Benign

0.037

Sift

Benign

0.35

T;T;T;T

Sift4G

Benign

0.36

T;T;T;T

Polyphen

0.0010

.;B;.;.

Vest4

0.25

MVP

0.41

MPC

0.37

ClinPred

0.027

GERP RS

3.9

Varity_R

0.029

gMVP

0.40

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over