chr2-119809969-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002830.4(PTPN4):​c.116C>G​(p.Thr39Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000412 in 1,456,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T39A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

PTPN4
NM_002830.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.62
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.23441947).
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTPN4NM_002830.4 linkc.116C>G p.Thr39Ser missense_variant Exon 2 of 27 ENST00000263708.7 NP_002821.1 P29074

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTPN4ENST00000263708.7 linkc.116C>G p.Thr39Ser missense_variant Exon 2 of 27 1 NM_002830.4 ENSP00000263708.2 P29074

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000412
AC:
6
AN:
1456120
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
724106
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00000360
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Nov 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.116C>G (p.T39S) alteration is located in exon 2 (coding exon 1) of the PTPN4 gene. This alteration results from a C to G substitution at nucleotide position 116, causing the threonine (T) at amino acid position 39 to be replaced by a serine (S). 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
0.097
BayesDel_addAF
Benign
-0.069
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.25
T;.;.
Eigen
Benign
-0.22
Eigen_PC
Benign
0.0060
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.76
T;T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.23
T;T;T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
0.47
N;.;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-1.2
N;N;N
REVEL
Benign
0.18
Sift
Benign
0.43
T;T;T
Sift4G
Benign
0.38
T;T;T
Polyphen
0.0050
B;.;.
Vest4
0.34
MutPred
0.62
Gain of disorder (P = 0.1237);Gain of disorder (P = 0.1237);Gain of disorder (P = 0.1237);
MVP
0.49
MPC
0.42
ClinPred
0.56
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.13
gMVP
0.33

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.

Other links and lift over

dbSNP: rs1247625783; hg19: chr2-120567545; API