rs2401751

Positions:

• chr14-88480278-G-A
• chr14-88480278-G-T

Variant summary

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

The NM_007039.4(PTPN21):​c.1153C>T​(p.Leu385Phe) variant causes a missense change. The variant allele was found at a frequency of 0.334 in 1,613,658 control chromosomes in the GnomAD database, including 91,718 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 0.34 (8804 hom., cov: 32)
  • Exomes 𝑓: 0.33 (82914 hom.)
• Consequence: PTPN21 NM_007039.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.65

Genes affected

PTPN21 (HGNC:9651): (protein tyrosine phosphatase non-receptor type 21) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains an N-terminal domain, similar to cytoskeletal- associated proteins including band 4.1, ezrin, merlin, and radixin. This PTP was shown to specially interact with BMX/ETK, a member of Tec tyrosine kinase family characterized by a multimodular structures including PH, SH3, and SH2 domains. The interaction of this PTP with BMX kinase was found to increase the activation of STAT3, but not STAT2 kinase. Studies of the similar gene in mice suggested the possible roles of this PTP in liver regeneration and spermatogenesis. [provided by RefSeq, Jul 2008]

PTPN21 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00300166).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN21	NM_007039.4	c.1153C>T	p.Leu385Phe	missense_variant	13/19	ENST00000556564.6	NP_008970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN21	ENST00000556564.6	c.1153C>T	p.Leu385Phe	missense_variant	13/19	1	NM_007039.4	ENSP00000452414.1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51164 AN: 151956 Hom.: 8786 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.310

GnomAD3 exomes AF: 0.324 AC: 81337 AN: 251188 Hom.: 13592 AF XY: 0.327 AC XY: 44398 AN XY: 135736

Gnomad AFR exome AF: 0.375

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.333

Gnomad EAS exome AF: 0.332

Gnomad SAS exome AF: 0.393

Gnomad FIN exome AF: 0.279

Gnomad NFE exome AF: 0.336

Gnomad OTH exome AF: 0.305

GnomAD4 exome AF: 0.334 AC: 488395 AN: 1461584 Hom.: 82914 Cov.: 51 AF XY: 0.336 AC XY: 244256 AN XY: 727110

Gnomad4 AFR exome AF: 0.376

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.326

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.283

Gnomad4 NFE exome AF: 0.336

Gnomad4 OTH exome AF: 0.335

GnomAD4 genome AF: 0.337 AC: 51246 AN: 152074 Hom.: 8804 Cov.: 32 AF XY: 0.332 AC XY: 24701 AN XY: 74328

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.314

Alfa AF: 0.333 Hom.: 21305

Bravo AF: 0.333

TwinsUK AF: 0.328 AC: 1217

ALSPAC AF: 0.336 AC: 1296

ESP6500AA AF: 0.371 AC: 1636

ESP6500EA AF: 0.341 AC: 2931

ExAC AF: 0.331 AC: 40178

Asia WGS AF: 0.381 AC: 1325 AN: 3478

EpiCase AF: 0.326

EpiControl AF: 0.322

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.023	T;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.65	T;.
MetaRNN	Benign	0.0030	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.52	N;N
REVEL	Benign	0.14
Sift	Benign	0.26	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.24	B;B
Vest4		0.034
MPC		0.36
ClinPred		0.022	T
GERP RS		0.97
Varity_R		0.023

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: rs2401751; hg19: chr14-88946622; COSMIC: COSV60848288;