14-88479045-T-G

Position:

chr14-88479045-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007039.4(PTPN21):c.2386A>C(p.Met796Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,607,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

PTPN21
NM_007039.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.13

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.10590044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN21	NM_007039.4 linkuse as main transcript	c.2386A>C	p.Met796Leu	missense_variant	13/19	ENST00000556564.6	NP_008970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PTPN21	ENST00000556564.6 linkuse as main transcript	c.2386A>C	p.Met796Leu	missense_variant	13/19	1	NM_007039.4	ENSP00000452414	P1
PTPN21	ENST00000328736.7 linkuse as main transcript	c.2386A>C	p.Met796Leu	missense_variant	12/18	1		ENSP00000330276	P1
PTPN21	ENST00000554270.5 linkuse as main transcript	n.2499A>C		non_coding_transcript_exon_variant	12/17	1
PTPN21	ENST00000536337.5 linkuse as main transcript	c.*2323A>C		3_prime_UTR_variant, NMD_transcript_variant	13/19	1		ENSP00000443951

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000696

AC:

AN:

244400

Hom.:

AF XY:

0.0000753

AC XY:

AN XY:

132762

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000118

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000117

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000112

AC:

163

AN:

1455142

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

723674

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000904

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000140

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2022

The c.2386A>C (p.M796L) alteration is located in exon 13 (coding exon 12) of the PTPN21 gene. This alteration results from a A to C substitution at nucleotide position 2386, causing the methionine (M) at amino acid position 796 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.56

DEOGEN2

Benign

0.0091

T;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.50

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.74

T;.

M_CAP

Benign

0.020

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

0.98

N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.081

Sift

Benign

0.14

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.0030

B;B

Vest4

0.42

MutPred

0.20

Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);

MVP

0.54

MPC

0.29

ClinPred

0.042

GERP RS

3.2

Varity_R

0.089

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over