chr14-88480278-G-A

Variant names:

• chr14-88480278-G-A
• rs2401751
• NM_007039.4:c.1153C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000556564.6(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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (8804 hom., cov: 32)
  • Exomes 𝑓: 0.33 (82914 hom.)
• Consequence: PTPN21 ENST00000556564.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.65
• Publications: 39 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000556564.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN21	NM_007039.4	MANE Select	c.1153C>T	p.Leu385Phe	missense	Exon 13 of 19	NP_008970.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN21	ENST00000556564.6	TSL:1 MANE Select	c.1153C>T	p.Leu385Phe	missense	Exon 13 of 19	ENSP00000452414.1
	PTPN21	ENST00000328736.7	TSL:1	c.1153C>T	p.Leu385Phe	missense	Exon 12 of 18	ENSP00000330276.3
	PTPN21	ENST00000536337.5	TSL:1	n.*1090C>T		non_coding_transcript_exon	Exon 13 of 19	ENSP00000443951.1

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

GnomAD2 exomes AF: 0.324 AC: 81337 AN: 251188 AF XY: 0.327

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 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

African (AFR) AF: 0.376 AC: 12572 AN: 33472

American (AMR) AF: 0.231 AC: 10342 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 8711 AN: 26134

East Asian (EAS) AF: 0.326 AC: 12935 AN: 39700

South Asian (SAS) AF: 0.389 AC: 33564 AN: 86242

European-Finnish (FIN) AF: 0.283 AC: 15126 AN: 53406

Middle Eastern (MID) AF: 0.252 AC: 1456 AN: 5768

European-Non Finnish (NFE) AF: 0.336 AC: 373439 AN: 1111748

Other (OTH) AF: 0.335 AC: 20250 AN: 60394

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

African (AFR) AF: 0.367 AC: 15215 AN: 41454

American (AMR) AF: 0.259 AC: 3957 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3472

East Asian (EAS) AF: 0.344 AC: 1779 AN: 5168

South Asian (SAS) AF: 0.419 AC: 2017 AN: 4818

European-Finnish (FIN) AF: 0.284 AC: 3002 AN: 10578

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.339 AC: 23053 AN: 67966

Other (OTH) AF: 0.314 AC: 664 AN: 2116

Alfa AF: 0.335 Hom.: 29897

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 v4.9

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
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
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.7
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.14
Sift	Benign	0.26	T
Sift4G	Benign	0.54	T
Polyphen		0.24	B
Vest4		0.034
MPC		0.36
ClinPred		0.022	T
GERP RS		0.97
Varity_R		0.023
Mutation Taster		=100/0	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: rs2401751; hg19: chr14-88946622; COSMIC: COSV60848288;