rs12500797

chr4-86771240-G-Achr4-86771240-G-C

Variant summary

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

The NM_080683.3(PTPN13):c.4873G>A(p.Glu1625Lys) variant causes a missense change. The variant allele was found at a frequency of 0.101 in 1,610,342 control chromosomes in the GnomAD database, including 9,232 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 0.078 (635 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8597 hom.)
• Consequence: PTPN13 NM_080683.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.35

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=0.002289176).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN13	NM_080683.3	c.4873G>A	p.Glu1625Lys	missense_variant	31/48	ENST00000411767.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN13	ENST00000411767.7	c.4873G>A	p.Glu1625Lys	missense_variant	31/48	1	NM_080683.3	P4

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11810 AN: 152050 Hom.: 633 Cov.: 32

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0777

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.0511

Gnomad FIN AF: 0.0787

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0872

GnomAD3 exomes AF: 0.0793 AC: 19228 AN: 242542 Hom.: 903 AF XY: 0.0814 AC XY: 10678 AN XY: 131116

Gnomad AFR exome AF: 0.0245

Gnomad AMR exome AF: 0.0465

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.0127

Gnomad SAS exome AF: 0.0506

Gnomad FIN exome AF: 0.0776

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.0928

GnomAD4 exome AF: 0.103 AC: 150891 AN: 1458174 Hom.: 8597 Cov.: 32 AF XY: 0.102 AC XY: 74029 AN XY: 724794

Gnomad4 AFR exome AF: 0.0235

Gnomad4 AMR exome AF: 0.0500

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.00894

Gnomad4 SAS exome AF: 0.0502

Gnomad4 FIN exome AF: 0.0798

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.0986

GnomAD4 genome AF: 0.0776 AC: 11810 AN: 152168 Hom.: 635 Cov.: 32 AF XY: 0.0747 AC XY: 5556 AN XY: 74386

Gnomad4 AFR AF: 0.0272

Gnomad4 AMR AF: 0.0775

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.0116

Gnomad4 SAS AF: 0.0510

Gnomad4 FIN AF: 0.0787

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0863

Alfa AF: 0.102 Hom.: 1364

Bravo AF: 0.0762

TwinsUK AF: 0.125 AC: 463

ALSPAC AF: 0.114 AC: 441

ESP6500AA AF: 0.0301 AC: 119

ESP6500EA AF: 0.120 AC: 1002

ExAC AF: 0.0777 AC: 9393

Asia WGS AF: 0.0330 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.40
Cadd	Uncertain	24
Dann	Benign	0.97
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T;T;T;T;.
MetaRNN	Benign	0.0023	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.036	P;P;P;P;P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.7	N;N;N;N;N
REVEL	Benign	0.061
Sift	Benign	0.10	T;T;T;T;T
Sift4G	Benign	0.20	T;T;T;T;T
Polyphen		0.21	B;B;P;B;B
Vest4		0.18
MPC		0.081
ClinPred		0.026	T
GERP RS		5.3
Varity_R		0.13
gMVP		0.34

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: rs12500797; hg19: chr4-87692393;