14-88480278-G-T

Position:

• chr14-88480278-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007039.4(PTPN21):​c.1153C>A​(p.Leu385Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L385F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11053884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN21	NM_007039.4	c.1153C>A	p.Leu385Ile	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>A	p.Leu385Ile	missense_variant	13/19	1	NM_007039.4	ENSP00000452414.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.84
DEOGEN2	Benign	0.017	T;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.73
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	T;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.15	N;N
REVEL	Benign	0.11
Sift	Benign	0.19	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.042	B;B
Vest4		0.20
MutPred		0.41		Loss of solvent accessibility (P = 0.0404);Loss of solvent accessibility (P = 0.0404);
MVP		0.52
MPC		0.35
ClinPred		0.13	T
GERP RS		0.97
Varity_R		0.028

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;