Variant 11-18729538-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006906.2(PTPN5):c.1519A>C(p.Ile507Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000239 in 1,599,632 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

PTPN5
NM_006906.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.93

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:

IGSF22-AS1 (HGNC:55511): (IGSF22 antisense RNA 1)

IGSF22-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN5	NM_006906.2 linkuse as main transcript	c.1519A>C	p.Ile507Leu	missense_variant	14/15	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.1519A>C	p.Ile507Leu	missense_variant	14/15	1	NM_006906.2	ENSP00000351342		P54829-1
IGSF22-AS1	ENST00000527285.1 linkuse as main transcript	n.730-10886T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.000324

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000198

AC:

AN:

242620

Hom.:

AF XY:

0.000219

AC XY:

AN XY:

132198

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000337

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000243

AC:

351

AN:

1447410

Hom.:

Cov.:

AF XY:

0.000258

AC XY:

186

AN XY:

720854

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000226

Gnomad4 NFE exome

AF:

0.000298

Gnomad4 OTH exome

AF:

0.0000832

GnomAD4 genome

AF:

0.000210

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000324

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000281

Hom.:

Bravo

AF:

0.000317

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000652

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

May 27, 2022

The c.1519A>C (p.I507L) alteration is located in exon 14 (coding exon 13) of the PTPN5 gene. This alteration results from a A to C substitution at nucleotide position 1519, causing the isoleucine (I) at amino acid position 507 to be replaced by a leucine (L). 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

.;T;T;.;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

D;D;D;D;D

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.49

T;T;T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

2.0

.;M;.;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.8

N;N;N;N;N

REVEL

Uncertain

0.33

Sift

Uncertain

0.0030

D;D;D;D;D

Sift4G

Uncertain

0.038

D;D;T;D;D

Polyphen

0.80

.;P;.;.;.

Vest4

0.79

MVP

0.72

MPC

1.0

ClinPred

0.21

GERP RS

4.3

Varity_R

0.79

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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