rs4978813

Variant names:

• chr9-109489283-G-A
• rs4978813
• NM_002829.4:c.-18+8936C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-109489283-G-A
• chr9-109489283-G-C
• chr9-109489283-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN3	NM_002829.4	MANE Select	c.-18+8936C>T		intron	N/A	NP_002820.3
	PTPN3	NM_001145368.2		c.-18+8936C>T		intron	N/A	NP_001138840.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN3	ENST00000374541.4	TSL:5 MANE Select	c.-18+8936C>T		intron	N/A	ENSP00000363667.1
	PTPN3	ENST00000262539.7	TSL:5	c.-18+8936C>T		intron	N/A	ENSP00000262539.4

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

African (AFR) AF: 0.506 AC: 20969 AN: 41452

American (AMR) AF: 0.581 AC: 8881 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2321 AN: 3468

East Asian (EAS) AF: 0.891 AC: 4593 AN: 5154

South Asian (SAS) AF: 0.622 AC: 2996 AN: 4820

European-Finnish (FIN) AF: 0.426 AC: 4498 AN: 10570

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35556 AN: 67950

Other (OTH) AF: 0.574 AC: 1209 AN: 2108

Alfa AF: 0.539 Hom.: 63954

Bravo AF: 0.551

Asia WGS AF: 0.689 AC: 2399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.51
PhyloP100		-0.36
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: rs4978813; hg19: chr9-112251563;