chr4-86764643-T-G

Position:

• chr4-86764643-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.4068T>G​(p.Phe1356Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,582,100 control chromosomes in the GnomAD database, including 9,112 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.084 (681 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8431 hom.)
• Consequence: PTPN13 NM_080683.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.65

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]

PTPN13 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001401037).
• 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	Protein	UniProt
PTPN13	NM_080683.3	c.4068T>G	p.Phe1356Leu	missense_variant	25/48	ENST00000411767.7	NP_542414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN13	ENST00000411767.7	c.4068T>G	p.Phe1356Leu	missense_variant	25/48	1	NM_080683.3	ENSP00000407249.2

Frequencies

GnomAD3 genomes AF: 0.0837 AC: 12730 AN: 152156 Hom.: 679 Cov.: 32

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0832

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.0488

Gnomad FIN AF: 0.0786

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0927

GnomAD3 exomes AF: 0.0796 AC: 16891 AN: 212188 Hom.: 797 AF XY: 0.0812 AC XY: 9267 AN XY: 114130

Gnomad AFR exome AF: 0.0465

Gnomad AMR exome AF: 0.0472

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.0126

Gnomad SAS exome AF: 0.0463

Gnomad FIN exome AF: 0.0761

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.0895

GnomAD4 exome AF: 0.104 AC: 148426 AN: 1429826 Hom.: 8431 Cov.: 30 AF XY: 0.102 AC XY: 72587 AN XY: 709146

Gnomad4 AFR exome AF: 0.0449

Gnomad4 AMR exome AF: 0.0519

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.00876

Gnomad4 SAS exome AF: 0.0477

Gnomad4 FIN exome AF: 0.0792

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.0998

GnomAD4 genome AF: 0.0836 AC: 12735 AN: 152274 Hom.: 681 Cov.: 32 AF XY: 0.0805 AC XY: 5993 AN XY: 74456

Gnomad4 AFR AF: 0.0474

Gnomad4 AMR AF: 0.0830

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0116

Gnomad4 SAS AF: 0.0486

Gnomad4 FIN AF: 0.0786

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.107 Hom.: 1724

Bravo AF: 0.0838

TwinsUK AF: 0.122 AC: 454

ALSPAC AF: 0.116 AC: 447

ESP6500AA AF: 0.0534 AC: 192

ESP6500EA AF: 0.120 AC: 974

ExAC AF: 0.0757 AC: 9115

Asia WGS AF: 0.0340 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Benign	0.86
DEOGEN2	Benign	0.059	.;.;.;T;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.57	T;T;T;T;.
MetaRNN	Benign	0.0014	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L;.;L;L
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.89	N;N;N;N;N
REVEL	Benign	0.047
Sift	Benign	0.32	T;T;T;T;T
Sift4G	Benign	0.95	T;T;T;T;T
Polyphen		0.0010	B;B;B;B;B
Vest4		0.046
MutPred		0.099		.;Loss of glycosylation at P1360 (P = 0.0217);.;Loss of glycosylation at P1360 (P = 0.0217);Loss of glycosylation at P1360 (P = 0.0217);
MPC		0.038
ClinPred		0.0042	T
GERP RS		1.2
Varity_R		0.059
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10033029; hg19: chr4-87685796; COSMIC: COSV57410377; COSMIC: COSV57410377;