rs12500797

Variant names:

• chr4-86771240-G-A
• rs12500797
• NM_080683.3:c.4873G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-86771240-G-A
• chr4-86771240-G-C

Variant summary

Our verdict is Benign. The variant received -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. 12/21 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 0.078 (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
• Publications: 18 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=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 rank	MANE	Protein	UniProt
PTPN13	NM_080683.3	c.4873G>A	p.Glu1625Lys	missense_variant	Exon 31 of 48	ENST00000411767.7	NP_542414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN13	ENST00000411767.7	c.4873G>A	p.Glu1625Lys	missense_variant	Exon 31 of 48	1	NM_080683.3	ENSP00000407249.2

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

GnomAD2 exomes AF: 0.0793 AC: 19228 AN: 242542 AF XY: 0.0814

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 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

African (AFR) AF: 0.0235 AC: 785 AN: 33448

American (AMR) AF: 0.0500 AC: 2215 AN: 44276

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3115 AN: 26050

East Asian (EAS) AF: 0.00894 AC: 354 AN: 39604

South Asian (SAS) AF: 0.0502 AC: 4281 AN: 85246

European-Finnish (FIN) AF: 0.0798 AC: 4251 AN: 53256

Middle Eastern (MID) AF: 0.0692 AC: 399 AN: 5766

European-Non Finnish (NFE) AF: 0.117 AC: 129549 AN: 1110252

Other (OTH) AF: 0.0986 AC: 5942 AN: 60276

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

African (AFR) AF: 0.0272 AC: 1130 AN: 41504

American (AMR) AF: 0.0775 AC: 1185 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 393 AN: 3470

East Asian (EAS) AF: 0.0116 AC: 60 AN: 5186

South Asian (SAS) AF: 0.0510 AC: 246 AN: 4826

European-Finnish (FIN) AF: 0.0787 AC: 833 AN: 10582

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7708 AN: 68002

Other (OTH) AF: 0.0863 AC: 182 AN: 2110

Alfa AF: 0.0993 Hom.: 2741

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
DEOGEN2	Benign	0.0	.;.;.;T;.
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
MutationAssessor	Benign	0.0	.;.;.;M;.
PhyloP100		5.4
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
Vest4		0.18
ClinPred		0.026	T
GERP RS		5.3
Varity_R		0.13
gMVP		0.34
Mutation Taster		=94/6	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: rs12500797; hg19: chr4-87692393; COSMIC: COSV107347511; COSMIC: COSV107347511;