9-109382353-T-C

Variant names:

• chr9-109382353-T-C
• NM_002829.4:c.2477A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002829.4(PTPN3):​c.2477A>G​(p.Asn826Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTPN3 NM_002829.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0860

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]

ACMG classification

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=0.101124436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN3	NM_002829.4	c.2477A>G	p.Asn826Ser	missense_variant	Exon 24 of 26	ENST00000374541.4	NP_002820.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN3	ENST00000374541.4	c.2477A>G	p.Asn826Ser	missense_variant	Exon 24 of 26	5	NM_002829.4	ENSP00000363667.1
PTPN3	ENST00000412145.5	c.2084A>G	p.Asn695Ser	missense_variant	Exon 19 of 21	1		ENSP00000416654.1
PTPN3	ENST00000446349.5	c.1949A>G	p.Asn650Ser	missense_variant	Exon 18 of 20	1		ENSP00000395384.1
PTPN3	ENST00000262539	c.*73A>G		3_prime_UTR_variant	Exon 24 of 26	5		ENSP00000262539.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2477A>G (p.N826S) alteration is located in exon 24 (coding exon 23) of the PTPN3 gene. This alteration results from a A to G substitution at nucleotide position 2477, causing the asparagine (N) at amino acid position 826 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	0.073
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.86
DEOGEN2	Benign	0.24	.;.;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.030	.;.;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.38	N;N;N
REVEL	Benign	0.23
Sift	Benign	0.72	T;T;T
Sift4G	Benign	0.74	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.12
MutPred		0.64		.;.;Gain of phosphorylation at N826 (P = 0.0545);
MVP		0.65
MPC		0.18
ClinPred		0.072	T
GERP RS		2.9
Varity_R		0.12
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr9-112144633;