chr9-109457194-C-G

Position:

• chr9-109457194-C-G

Variant summary

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

The NM_002829.4(PTPN3):​c.268G>C​(p.Ala90Pro) variant causes a missense change. The variant allele was found at a frequency of 0.353 in 1,613,064 control chromosomes in the GnomAD database, including 103,209 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.38 (11430 hom., cov: 33)
  • Exomes 𝑓: 0.35 (91779 hom.)
• Consequence: PTPN3 NM_002829.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.93

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 (MetaRNN=9.1424584E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN3	NM_002829.4	c.268G>C	p.Ala90Pro	missense_variant	4/26	ENST00000374541.4	NP_002820.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN3	ENST00000374541.4	c.268G>C	p.Ala90Pro	missense_variant	4/26	5	NM_002829.4	ENSP00000363667	P1
PTPN3	ENST00000262539.7	c.268G>C	p.Ala90Pro	missense_variant	4/26	5		ENSP00000262539

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57423 AN: 151984 Hom.: 11402 Cov.: 33

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.357

GnomAD3 exomes AF: 0.346 AC: 86913 AN: 251060 Hom.: 15692 AF XY: 0.351 AC XY: 47654 AN XY: 135668

Gnomad AFR exome AF: 0.493

Gnomad AMR exome AF: 0.247

Gnomad ASJ exome AF: 0.313

Gnomad EAS exome AF: 0.352

Gnomad SAS exome AF: 0.433

Gnomad FIN exome AF: 0.306

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.328

GnomAD4 exome AF: 0.351 AC: 512375 AN: 1460962 Hom.: 91779 Cov.: 37 AF XY: 0.353 AC XY: 256410 AN XY: 726844

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.255

Gnomad4 ASJ exome AF: 0.312

Gnomad4 EAS exome AF: 0.378

Gnomad4 SAS exome AF: 0.436

Gnomad4 FIN exome AF: 0.307

Gnomad4 NFE exome AF: 0.345

Gnomad4 OTH exome AF: 0.354

GnomAD4 genome AF: 0.378 AC: 57499 AN: 152102 Hom.: 11430 Cov.: 33 AF XY: 0.375 AC XY: 27862 AN XY: 74348

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.358

Alfa AF: 0.350 Hom.: 7144

Bravo AF: 0.382

TwinsUK AF: 0.340 AC: 1262

ALSPAC AF: 0.347 AC: 1338

ESP6500AA AF: 0.482 AC: 2124

ESP6500EA AF: 0.339 AC: 2915

ExAC AF: 0.357 AC: 43295

Asia WGS AF: 0.406 AC: 1412 AN: 3478

EpiCase AF: 0.343

EpiControl AF: 0.346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.074
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.36	T;T
MetaRNN	Benign	0.00091	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-2.4	.;N
MutationTaster	Benign	0.83	P;P;P
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	3.8	.;N
REVEL	Uncertain	0.35
Sift	Benign	1.0	.;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	.;B
Vest4		0.065
MPC		0.29
ClinPred		0.019	T
GERP RS		5.6
Varity_R		0.23
gMVP		0.33

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: rs3793524; hg19: chr9-112219474; COSMIC: COSV52704718;