Variant chr14-88469683-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_007039.4(PTPN21):c.3051G>A(p.Arg1017=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00791 in 1,614,138 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0064 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 63 hom. )

Consequence

PTPN21
NM_007039.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0870

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:

SPATA7 (HGNC:20423): (spermatogenesis associated 7) This gene, originally isolated from testis, is also expressed in retina. Mutations in this gene are associated with Leber congenital amaurosis and juvenile retinitis pigmentosa. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

SPATA7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 14-88469683-C-T is Benign according to our data. Variant chr14-88469683-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2644435.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.087 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN21	NM_007039.4 linkuse as main transcript	c.3051G>A	p.Arg1017=	synonymous_variant	17/19	ENST00000556564.6	NP_008970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN21	ENST00000556564.6 linkuse as main transcript	c.3051G>A	p.Arg1017=	synonymous_variant	17/19	1	NM_007039.4	ENSP00000452414	P1

Frequencies

GnomAD3 genomes

AF:

0.00638

AC:

970

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00632

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00911

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00651

AC:

1637

AN:

251458

Hom.:

AF XY:

0.00660

AC XY:

897

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00668

Gnomad ASJ exome

AF:

0.00823

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.00467

Gnomad NFE exome

AF:

0.00947

Gnomad OTH exome

AF:

0.00766

GnomAD4 exome

AF:

0.00807

AC:

11794

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00790

AC XY:

5743

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00720

Gnomad4 ASJ exome

AF:

0.00712

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00257

Gnomad4 FIN exome

AF:

0.00449

Gnomad4 NFE exome

AF:

0.00920

Gnomad4 OTH exome

AF:

0.00838

GnomAD4 genome

AF:

0.00636

AC:

968

AN:

152252

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

464

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00632

Gnomad4 NFE

AF:

0.00911

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00804

Hom.:

Bravo

AF:

0.00666

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00867

EpiControl

AF:

0.0104

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

PTPN21: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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