rs989902

Positions:

• chr4-86785353-T-G

Variant summary

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

The NM_080683.3(PTPN13):​c.6241T>G​(p.Tyr2081Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,603,776 control chromosomes in the GnomAD database, including 152,871 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 0.52 (22507 hom., cov: 31)
  • Exomes 𝑓: 0.42 (130364 hom.)
• Consequence: PTPN13 NM_080683.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399

Genes affected

PTPN13 (HGNC:9646): (protein tyrosine phosphatase non-receptor type 13) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP is a large intracellular protein. It has a catalytic PTP domain at its C-terminus and two major structural domains: a region with five PDZ domains and a FERM domain that binds to plasma membrane and cytoskeletal elements. This PTP was found to interact with, and dephosphorylate, Fas receptor and IkappaBalpha through the PDZ domains. This suggests it has a role in Fas mediated programmed cell death. This PTP was also shown to interact with GTPase-activating protein, and thus may function as a regulator of Rho signaling pathways. Four alternatively spliced transcript variants, which encode distinct proteins, have been reported. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.943122E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN13	NM_080683.3	c.6241T>G	p.Tyr2081Asp	missense_variant	39/48	ENST00000411767.7	NP_542414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN13	ENST00000411767.7	c.6241T>G	p.Tyr2081Asp	missense_variant	39/48	1	NM_080683.3	ENSP00000407249.2

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78640 AN: 151704 Hom.: 22467 Cov.: 31

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.500

GnomAD3 exomes AF: 0.424 AC: 104181 AN: 245716 Hom.: 23619 AF XY: 0.411 AC XY: 54829 AN XY: 133282

Gnomad AFR exome AF: 0.790

Gnomad AMR exome AF: 0.419

Gnomad ASJ exome AF: 0.468

Gnomad EAS exome AF: 0.410

Gnomad SAS exome AF: 0.269

Gnomad FIN exome AF: 0.435

Gnomad NFE exome AF: 0.414

Gnomad OTH exome AF: 0.425

GnomAD4 exome AF: 0.416 AC: 604261 AN: 1451954 Hom.: 130364 Cov.: 34 AF XY: 0.411 AC XY: 296848 AN XY: 722366

Gnomad4 AFR exome AF: 0.792

Gnomad4 AMR exome AF: 0.422

Gnomad4 ASJ exome AF: 0.472

Gnomad4 EAS exome AF: 0.421

Gnomad4 SAS exome AF: 0.269

Gnomad4 FIN exome AF: 0.433

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.441

GnomAD4 genome AF: 0.519 AC: 78734 AN: 151822 Hom.: 22507 Cov.: 31 AF XY: 0.515 AC XY: 38209 AN XY: 74194

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.500

Alfa AF: 0.433 Hom.: 36303

Bravo AF: 0.536

TwinsUK AF: 0.412 AC: 1529

ALSPAC AF: 0.407 AC: 1568

ESP6500AA AF: 0.784 AC: 2899

ESP6500EA AF: 0.420 AC: 3432

ExAC AF: 0.427 AC: 51610

Asia WGS AF: 0.366 AC: 1275 AN: 3478

EpiCase AF: 0.416

EpiControl AF: 0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.2
DANN	Benign	0.58
DEOGEN2	Benign	0.038	.;.;.;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.015	T;T;T;T;.
MetaRNN	Benign	0.0000019	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.6	.;.;.;N;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.3	N;N;N;N;N
REVEL	Benign	0.060
Sift	Benign	0.23	T;T;T;T;T
Sift4G	Benign	0.21	T;T;T;T;T
Polyphen		0.0	B;B;B;B;B
Vest4		0.040
MPC		0.049
ClinPred		0.0087	T
GERP RS		2.8
Varity_R		0.043
gMVP		0.16

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: rs989902; hg19: chr4-87706506; COSMIC: COSV57415600;