rs10521094

Variant names:

• chr9-109424357-A-G
• rs10521094
• NM_002829.4:c.1002-1505T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002829.4(PTPN3):​c.1002-1505T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 152,296 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.030 (121 hom., cov: 33)
• Consequence: PTPN3 NM_002829.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661
• Publications: 2 publications found

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]

PTPN3 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002829.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN3	NM_002829.4	MANE Select	c.1002-1505T>C		intron	N/A	NP_002820.3
	PTPN3	NM_001145368.2		c.1001+2593T>C		intron	N/A	NP_001138840.1	B7Z9V1
	PTPN3	NM_001145369.2		c.609-1505T>C		intron	N/A	NP_001138841.1	P26045-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN3	ENST00000374541.4	TSL:5 MANE Select	c.1002-1505T>C		intron	N/A	ENSP00000363667.1	P26045-1
	PTPN3	ENST00000412145.5	TSL:1	c.609-1505T>C		intron	N/A	ENSP00000416654.1	P26045-2
	PTPN3	ENST00000446349.5	TSL:1	c.608+2593T>C		intron	N/A	ENSP00000395384.1	P26045-3

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 4541 AN: 152178 Hom.: 121 Cov.: 33

Gnomad AFR AF: 0.00572

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.0462

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0421

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0299 AC: 4548 AN: 152296 Hom.: 121 Cov.: 33 AF XY: 0.0314 AC XY: 2339 AN XY: 74476

African (AFR) AF: 0.00570 AC: 237 AN: 41578

American (AMR) AF: 0.0733 AC: 1121 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0462 AC: 160 AN: 3466

East Asian (EAS) AF: 0.151 AC: 782 AN: 5172

South Asian (SAS) AF: 0.0251 AC: 121 AN: 4826

European-Finnish (FIN) AF: 0.0183 AC: 194 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0270 AC: 1834 AN: 68020

Other (OTH) AF: 0.0421 AC: 89 AN: 2112

Alfa AF: 0.0293 Hom.: 8

Bravo AF: 0.0335

Asia WGS AF: 0.0660 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.45
DANN	Benign	0.83
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10521094; hg19: chr9-112186637;