chr14-88472308-A-G

Position:

• chr14-88472308-A-G

Variant summary

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

The NM_007039.4(PTPN21):​c.2807T>C​(p.Val936Ala) variant causes a missense change. The variant allele was found at a frequency of 0.342 in 1,612,314 control chromosomes in the GnomAD database, including 96,549 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 0.37 (11193 hom., cov: 31)
  • Exomes 𝑓: 0.34 (85356 hom.)
• Consequence: PTPN21 NM_007039.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05

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=0.0070250034).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN21	NM_007039.4	c.2807T>C	p.Val936Ala	missense_variant	15/19	ENST00000556564.6	NP_008970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN21	ENST00000556564.6	c.2807T>C	p.Val936Ala	missense_variant	15/19	1	NM_007039.4	ENSP00000452414.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56725 AN: 151724 Hom.: 11168 Cov.: 31

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.333

GnomAD3 exomes AF: 0.334 AC: 83909 AN: 251380 Hom.: 14648 AF XY: 0.334 AC XY: 45440 AN XY: 135880

Gnomad AFR exome AF: 0.507

Gnomad AMR exome AF: 0.229

Gnomad ASJ exome AF: 0.333

Gnomad EAS exome AF: 0.332

Gnomad SAS exome AF: 0.394

Gnomad FIN exome AF: 0.279

Gnomad NFE exome AF: 0.336

Gnomad OTH exome AF: 0.311

GnomAD4 exome AF: 0.338 AC: 493855 AN: 1460472 Hom.: 85356 Cov.: 33 AF XY: 0.339 AC XY: 246630 AN XY: 726650

Gnomad4 AFR exome AF: 0.508

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.326

Gnomad4 SAS exome AF: 0.390

Gnomad4 FIN exome AF: 0.283

Gnomad4 NFE exome AF: 0.336

Gnomad4 OTH exome AF: 0.344

GnomAD4 genome AF: 0.374 AC: 56822 AN: 151842 Hom.: 11193 Cov.: 31 AF XY: 0.368 AC XY: 27341 AN XY: 74200

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.337

Alfa AF: 0.341 Hom.: 22998

Bravo AF: 0.376

TwinsUK AF: 0.328 AC: 1216

ALSPAC AF: 0.336 AC: 1296

ESP6500AA AF: 0.506 AC: 2230

ESP6500EA AF: 0.341 AC: 2933

ExAC AF: 0.343 AC: 41644

Asia WGS AF: 0.390 AC: 1358 AN: 3478

EpiCase AF: 0.327

EpiControl AF: 0.323

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	18
DANN	Benign	0.82
DEOGEN2	Benign	0.089	T;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.49	T;.
MetaRNN	Benign	0.0070	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.99	N;N
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	1.1	N;N
REVEL	Benign	0.12
Sift	Benign	0.37	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.0	B;B
Vest4		0.048
MPC		0.37
ClinPred		0.0086	T
GERP RS		5.9
Varity_R		0.025

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: rs2274736; hg19: chr14-88938652; COSMIC: COSV60848431; COSMIC: COSV60848431;