NM_006906.2:c.1085A>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006906.2(PTPN5):​c.1085A>T​(p.Tyr362Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y362C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

PTPN5
NM_006906.2 missense

Scores

2
8
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.81
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]
IGSF22-AS1 (HGNC:55511): (IGSF22 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.931

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTPN5NM_006906.2 linkc.1085A>T p.Tyr362Phe missense_variant Exon 11 of 15 ENST00000358540.7 NP_008837.1 P54829-1Q86TL3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTPN5ENST00000358540.7 linkc.1085A>T p.Tyr362Phe missense_variant Exon 11 of 15 1 NM_006906.2 ENSP00000351342.2 P54829-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.019
T
BayesDel_noAF
Benign
-0.27
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.51
.;D;.;.
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.89
D;D;D;D
M_CAP
Benign
0.016
T
MetaRNN
Pathogenic
0.93
D;D;D;D
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.92
.;L;.;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Uncertain
-3.5
D;D;D;D
REVEL
Uncertain
0.34
Sift
Benign
0.071
T;D;D;D
Sift4G
Benign
0.13
T;T;T;T
Polyphen
0.86
.;P;.;.
Vest4
0.77
MutPred
0.85
.;Loss of ubiquitination at K367 (P = 0.0583);.;.;
MVP
0.59
MPC
0.96
ClinPred
0.97
D
GERP RS
5.4
Varity_R
0.59
gMVP
0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-18754915; API