rs10521094

Positions:

• chr9-109424357-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN3	NM_002829.4	c.1002-1505T>C		intron_variant		ENST00000374541.4	NP_002820.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN3	ENST00000374541.4	c.1002-1505T>C		intron_variant		5	NM_002829.4	ENSP00000363667.1
PTPN3	ENST00000412145.5	c.609-1505T>C		intron_variant		1		ENSP00000416654.1
PTPN3	ENST00000446349.5	c.608+2593T>C		intron_variant		1		ENSP00000395384.1
PTPN3	ENST00000262539.7	c.1002-1505T>C		intron_variant		5		ENSP00000262539.4

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

Gnomad4 AFR AF: 0.00570

Gnomad4 AMR AF: 0.0733

Gnomad4 ASJ AF: 0.0462

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.0251

Gnomad4 FIN AF: 0.0183

Gnomad4 NFE AF: 0.0270

Gnomad4 OTH AF: 0.0421

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.45
DANN	Benign	0.83

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

Other links and lift over

dbSNP: rs10521094; hg19: chr9-112186637;