rs2230600

Variant names:

• chr4-86769845-A-G
• rs2230600
• NM_080683.3:c.4566A>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.4566A>G​(p.Ile1522Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,613,134 control chromosomes in the GnomAD database, including 26,340 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 0.14 (2004 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24336 hom.)
• Consequence: PTPN13 NM_080683.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• Publications: 41 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=0.0040934086).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080683.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN13	NM_080683.3	MANE Select	c.4566A>G	p.Ile1522Met	missense	Exon 29 of 48	NP_542414.1	Q12923-1
	PTPN13	NM_080685.3		c.4581A>G	p.Ile1527Met	missense	Exon 29 of 48	NP_542416.1	Q12923-4
	PTPN13	NM_006264.3		c.4509A>G	p.Ile1503Met	missense	Exon 28 of 47	NP_006255.1	Q12923-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN13	ENST00000411767.7	TSL:1 MANE Select	c.4566A>G	p.Ile1522Met	missense	Exon 29 of 48	ENSP00000407249.2	Q12923-1
	PTPN13	ENST00000427191.6	TSL:1	c.4509A>G	p.Ile1503Met	missense	Exon 28 of 47	ENSP00000408368.2	Q12923-3
	PTPN13	ENST00000316707.10	TSL:1	c.3993A>G	p.Ile1331Met	missense	Exon 26 of 45	ENSP00000322675.6	Q12923-2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22000 AN: 152052 Hom.: 2001 Cov.: 32

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.150

GnomAD2 exomes AF: 0.183 AC: 45635 AN: 249064 AF XY: 0.178

Gnomad AFR exome AF: 0.0329

Gnomad AMR exome AF: 0.263

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.306

Gnomad FIN exome AF: 0.214

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.175 AC: 255831 AN: 1460964 Hom.: 24336 Cov.: 32 AF XY: 0.173 AC XY: 125816 AN XY: 726832

African (AFR) AF: 0.0306 AC: 1024 AN: 33476

American (AMR) AF: 0.252 AC: 11276 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 4027 AN: 26128

East Asian (EAS) AF: 0.348 AC: 13801 AN: 39686

South Asian (SAS) AF: 0.113 AC: 9754 AN: 86236

European-Finnish (FIN) AF: 0.211 AC: 11288 AN: 53386

Middle Eastern (MID) AF: 0.126 AC: 729 AN: 5768

European-Non Finnish (NFE) AF: 0.174 AC: 193758 AN: 1111212

Other (OTH) AF: 0.169 AC: 10174 AN: 60358

GnomAD4 genome AF: 0.145 AC: 22013 AN: 152170 Hom.: 2004 Cov.: 32 AF XY: 0.148 AC XY: 11030 AN XY: 74380

African (AFR) AF: 0.0369 AC: 1535 AN: 41548

American (AMR) AF: 0.207 AC: 3155 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 539 AN: 3472

East Asian (EAS) AF: 0.305 AC: 1577 AN: 5176

South Asian (SAS) AF: 0.124 AC: 596 AN: 4818

European-Finnish (FIN) AF: 0.217 AC: 2290 AN: 10572

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.173 AC: 11744 AN: 67998

Other (OTH) AF: 0.153 AC: 322 AN: 2106

Alfa AF: 0.163 Hom.: 8023

Bravo AF: 0.142

TwinsUK AF: 0.170 AC: 629

ALSPAC AF: 0.174 AC: 672

ESP6500AA AF: 0.0348 AC: 127

ESP6500EA AF: 0.163 AC: 1331

ExAC AF: 0.177 AC: 21410

Asia WGS AF: 0.179 AC: 623 AN: 3476

EpiCase AF: 0.168

EpiControl AF: 0.168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.27	N
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.14
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.025
Sift	Benign	0.22	T
Sift4G	Benign	0.22	T
Polyphen		0.076	B
Vest4		0.16
MPC		0.061
ClinPred		0.010	T
GERP RS		3.1
Varity_R		0.036
gMVP		0.12
Mutation Taster		=95/5	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: rs2230600; hg19: chr4-87690998; COSMIC: COSV57404858; COSMIC: COSV57404858;