rs4978813

chr9-109489283-G-Achr9-109489283-G-Cchr9-109489283-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002829.4(PTPN3):c.-18+8936C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,012 control chromosomes in the GnomAD database, including 22,529 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 0.54 (22529 hom., cov: 32)
• Consequence: PTPN3 NM_002829.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN3	NM_002829.4	c.-18+8936C>T		intron_variant		ENST00000374541.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN3	ENST00000374541.4	c.-18+8936C>T		intron_variant		5	NM_002829.4	P1
PTPN3	ENST00000262539.7	c.-18+8936C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81552 AN: 151894 Hom.: 22520 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.537 AC: 81608 AN: 152012 Hom.: 22529 Cov.: 32 AF XY: 0.539 AC XY: 40072 AN XY: 74292

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.891

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.574

Alfa AF: 0.544 Hom.: 28806

Bravo AF: 0.551

Asia WGS AF: 0.689 AC: 2399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.2
Dann	Benign	0.51

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: rs4978813; hg19: chr9-112251563;