rs140802922

Variant names:

• chr9-109389341-G-A
• rs140802922
• NM_002829.4:c.2145C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_002829.4(PTPN3):​c.2145C>T​(p.Ile715Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00939 in 1,613,942 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0071 (8 hom., cov: 33)
  • Exomes 𝑓: 0.0096 (108 hom.)
• Consequence: PTPN3 NM_002829.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.143
• Publications: 1 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 9-109389341-G-A is Benign according to our data. Variant chr9-109389341-G-A is described in ClinVar as Benign. ClinVar VariationId is 707948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.143 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 8 Unknown gene

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.2145C>T	p.Ile715Ile	synonymous	Exon 22 of 26	NP_002820.3
	PTPN3	NM_001145368.2		c.2010C>T	p.Ile670Ile	synonymous	Exon 21 of 25	NP_001138840.1	B7Z9V1
	PTPN3	NM_001145369.2		c.1752C>T	p.Ile584Ile	synonymous	Exon 17 of 21	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.2145C>T	p.Ile715Ile	synonymous	Exon 22 of 26	ENSP00000363667.1	P26045-1
	PTPN3	ENST00000412145.5	TSL:1	c.1752C>T	p.Ile584Ile	synonymous	Exon 17 of 21	ENSP00000416654.1	P26045-2
	PTPN3	ENST00000446349.5	TSL:1	c.1617C>T	p.Ile539Ile	synonymous	Exon 16 of 20	ENSP00000395384.1	P26045-3

Frequencies

GnomAD3 genomes AF: 0.00711 AC: 1083 AN: 152222 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00867

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00655 AC: 1645 AN: 251074 AF XY: 0.00682

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.00206

Gnomad ASJ exome AF: 0.000894

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0103

Gnomad NFE exome AF: 0.0107

Gnomad OTH exome AF: 0.00833

GnomAD4 exome AF: 0.00962 AC: 14066 AN: 1461604 Hom.: 108 Cov.: 30 AF XY: 0.00943 AC XY: 6860 AN XY: 727094

African (AFR) AF: 0.00134 AC: 45 AN: 33470

American (AMR) AF: 0.00204 AC: 91 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.000689 AC: 18 AN: 26134

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39698

South Asian (SAS) AF: 0.00203 AC: 175 AN: 86176

European-Finnish (FIN) AF: 0.0115 AC: 612 AN: 53416

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5762

European-Non Finnish (NFE) AF: 0.0114 AC: 12677 AN: 1111862

Other (OTH) AF: 0.00722 AC: 436 AN: 60390

GnomAD4 genome AF: 0.00711 AC: 1083 AN: 152338 Hom.: 8 Cov.: 33 AF XY: 0.00679 AC XY: 506 AN XY: 74490

African (AFR) AF: 0.00192 AC: 80 AN: 41574

American (AMR) AF: 0.00333 AC: 51 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4826

European-Finnish (FIN) AF: 0.00867 AC: 92 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0123 AC: 837 AN: 68032

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00978 Hom.: 7

Bravo AF: 0.00622

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00927

EpiControl AF: 0.0104

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.6
DANN	Benign	0.73
PhyloP100		0.14
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs140802922; hg19: chr9-112151621; COSMIC: COSV52711174;