rs989902

Variant names:

• chr4-86785353-T-G
• rs989902
• NM_080683.3:c.6241T>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 55 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PTPN13	NM_080683.3	c.6241T>G	p.Tyr2081Asp	missense_variant	Exon 39 of 48	ENST00000411767.7	NP_542414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN13	ENST00000411767.7	c.6241T>G	p.Tyr2081Asp	missense_variant	Exon 39 of 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

GnomAD2 exomes AF: 0.424 AC: 104181 AN: 245716 AF XY: 0.411

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 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

African (AFR) AF: 0.792 AC: 26360 AN: 33280

American (AMR) AF: 0.422 AC: 18685 AN: 44280

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 12270 AN: 26014

East Asian (EAS) AF: 0.421 AC: 16649 AN: 39532

South Asian (SAS) AF: 0.269 AC: 22989 AN: 85564

European-Finnish (FIN) AF: 0.433 AC: 23110 AN: 53312

Middle Eastern (MID) AF: 0.422 AC: 2423 AN: 5746

European-Non Finnish (NFE) AF: 0.412 AC: 455303 AN: 1104214

Other (OTH) AF: 0.441 AC: 26472 AN: 60012

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

African (AFR) AF: 0.780 AC: 32347 AN: 41458

American (AMR) AF: 0.470 AC: 7168 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1641 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2149 AN: 5166

South Asian (SAS) AF: 0.281 AC: 1352 AN: 4808

European-Finnish (FIN) AF: 0.439 AC: 4627 AN: 10536

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27887 AN: 67838

Other (OTH) AF: 0.500 AC: 1051 AN: 2102

Alfa AF: 0.449 Hom.: 57201

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;.
PhyloP100		0.40
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
Mutation Taster		=99/1	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: rs989902; hg19: chr4-87706506; COSMIC: COSV57415600;