rs769685005

Variant summary

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

The NM_002829.4(PTPN3):​c.2446G>T​(p.Asp816Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D816N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PTPN3
NM_002829.4 missense

Scores

8
10
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.90
Variant links:
Genes affected
PTPN3 (HGNC:9655): (protein tyrosine phosphatase non-receptor type 3) 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. P97, a cell cycle regulator involved in a variety of membrane related functions, has been shown to be a substrate of this PTP. This PTP was also found to interact with, and be regulated by adaptor protein 14-3-3 beta. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]

Genome browser will be placed here

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, 0.865

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTPN3NM_002829.4 linkc.2446G>T p.Asp816Tyr missense_variant Exon 24 of 26 ENST00000374541.4 NP_002820.3 P26045-1B7Z9V1Q8N4S3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTPN3ENST00000374541.4 linkc.2446G>T p.Asp816Tyr missense_variant Exon 24 of 26 5 NM_002829.4 ENSP00000363667.1 P26045-1
PTPN3ENST00000412145.5 linkc.2053G>T p.Asp685Tyr missense_variant Exon 19 of 21 1 ENSP00000416654.1 P26045-2
PTPN3ENST00000446349.5 linkc.1918G>T p.Asp640Tyr missense_variant Exon 18 of 20 1 ENSP00000395384.1 P26045-3
PTPN3ENST00000262539 linkc.*42G>T 3_prime_UTR_variant Exon 24 of 26 5 ENSP00000262539.4 J3KN34

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461796
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727206
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.58
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.76
.;.;D
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Uncertain
0.29
D
MetaRNN
Pathogenic
0.86
D;D;D
MetaSVM
Uncertain
0.53
D
MutationAssessor
Uncertain
2.1
.;.;M
PrimateAI
Uncertain
0.71
T
PROVEAN
Pathogenic
-7.6
D;D;D
REVEL
Pathogenic
0.77
Sift
Uncertain
0.0030
D;D;D
Sift4G
Uncertain
0.0050
D;D;D
Polyphen
0.99
.;.;D
Vest4
0.74
MutPred
0.58
.;.;Loss of disorder (P = 0.0185);
MVP
0.94
MPC
0.94
ClinPred
1.0
D
GERP RS
4.3
Varity_R
0.88
gMVP
0.66

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: chr9-112144664; API