Variant chr11-18729817-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.1331G>A(p.Ser444Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PTPN5
NM_006906.2 missense, splice_region

Scores

Splicing: ADA: 0.0002775

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 2.33

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08804572).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN5	NM_006906.2 linkuse as main transcript	c.1331G>A	p.Ser444Asn	missense_variant, splice_region_variant	13/15	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.1331G>A	p.Ser444Asn	missense_variant, splice_region_variant	13/15	1	NM_006906.2	ENSP00000351342		P54829-1
IGSF22-AS1	ENST00000527285.1 linkuse as main transcript	n.730-10607C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

247108

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134262

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

not provided, no classification provided

literature only

Psychiatry Genetics Yale University

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.099

.;T;T;.;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.74

T;T;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.080

T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

-0.24

.;N;.;.;.

MutationTaster

Benign

0.96

N;N;N;N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.30

T;T;T;T;T

Sift4G

Benign

0.45

T;T;T;T;T

Polyphen

0.0

.;B;.;.;.

Vest4

0.084

MVP

0.83

MPC

0.28

ClinPred

0.065

GERP RS

3.4

Varity_R

0.079

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00028

dbscSNV1_RF

Benign

0.028

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