2-119882508-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_002830.4(PTPN4):c.472C>A(p.Leu158Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,522,120 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 13 hom. )

Consequence

PTPN4
NM_002830.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.517

Variant links:

Genes affected

PTPN4 (HGNC:9656): (protein tyrosine phosphatase non-receptor type 4) 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 protein contains a C-terminal PTP domain and an N-terminal domain homologous to the band 4.1 superfamily of cytoskeletal-associated proteins. This PTP has been shown to interact with glutamate receptor delta 2 and epsilon subunits, and is thought to play a role in signalling downstream of the glutamate receptors through tyrosine dephosphorylation. [provided by RefSeq, Jul 2008]

PTPN4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019843102).

BP6

Variant 2-119882508-C-A is Benign according to our data. Variant chr2-119882508-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3043761.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00256 (390/152240) while in subpopulation NFE AF= 0.00484 (329/67988). AF 95% confidence interval is 0.00441. There are 0 homozygotes in gnomad4. There are 181 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 390 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN4	NM_002830.4 link	c.472C>A	p.Leu158Ile	missense_variant	Exon 8 of 27	ENST00000263708.7	NP_002821.1	P29074

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTPN4	ENST00000263708.7 link	c.472C>A	p.Leu158Ile	missense_variant	Exon 8 of 27	1	NM_002830.4	ENSP00000263708.2	P29074
PTPN4	ENST00000430976.5 link	n.4C>A		non_coding_transcript_exon_variant	Exon 1 of 20	5		ENSP00000395603.1	J3QT59
PTPN4	ENST00000433888.5 link	n.226C>A		non_coding_transcript_exon_variant	Exon 5 of 10	3		ENSP00000411364.1	J3QT89
PTPN4	ENST00000485247.1 link	n.519C>A		non_coding_transcript_exon_variant	Exon 7 of 7	3

Frequencies

GnomAD3 genomes

AF:

0.00256

AC:

390

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00484

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00223

AC:

353

AN:

157946

Hom.:

AF XY:

0.00211

AC XY:

177

AN XY:

84022

show subpopulations

Gnomad AFR exome

AF:

0.000531

Gnomad AMR exome

AF:

0.000803

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.000341

Gnomad NFE exome

AF:

0.00432

Gnomad OTH exome

AF:

0.00187

GnomAD4 exome

AF:

0.00408

AC:

5586

AN:

1369880

Hom.:

Cov.:

AF XY:

0.00397

AC XY:

2692

AN XY:

677674

show subpopulations

Gnomad4 AFR exome

AF:

0.000595

Gnomad4 AMR exome

AF:

0.000522

Gnomad4 ASJ exome

AF:

0.00167

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000878

Gnomad4 FIN exome

AF:

0.000436

Gnomad4 NFE exome

AF:

0.00493

Gnomad4 OTH exome

AF:

0.00330

GnomAD4 genome

AF:

0.00256

AC:

390

AN:

152240

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

181

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00484

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00427

Hom.:

Bravo

AF:

0.00264

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000687

AC:

ESP6500EA

AF:

0.00444

AC:

ExAC

AF:

0.00171

AC:

202

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PTPN4-related disorder

Benign:1

Apr 28, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.020

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.39

Sift

Uncertain

0.021

Sift4G

Uncertain

0.034

Polyphen

0.94

Vest4

0.35

MVP

0.60

MPC

1.4

ClinPred

0.025

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.30

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