14-88469683-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_007039.4(PTPN21):c.3051G>A(p.Arg1017Arg) 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

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

inherited retinal dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Leber congenital amaurosis 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
Leber congenital amaurosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
severe early-childhood-onset retinal dystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SPATA7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007039.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN21	NM_007039.4	MANE Select	c.3051G>A	p.Arg1017Arg	synonymous	Exon 17 of 19	NP_008970.2	Q16825

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPN21	ENST00000556564.6	TSL:1 MANE Select	c.3051G>A	p.Arg1017Arg	synonymous	Exon 17 of 19	ENSP00000452414.1	Q16825
PTPN21	ENST00000328736.7	TSL:1	c.3051G>A	p.Arg1017Arg	synonymous	Exon 16 of 18	ENSP00000330276.3	Q16825
PTPN21	ENST00000536337.5	TSL:1	n.*2988G>A		non_coding_transcript_exon	Exon 17 of 19	ENSP00000443951.1	G3V1Q9

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

GnomAD2 exomes

AF:

0.00651

AC:

1637

AN:

251458

AF XY:

0.00660

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 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

African (AFR)

AF:

0.00134

AC:

AN:

33480

American (AMR)

AF:

0.00720

AC:

322

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00712

AC:

186

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00257

AC:

222

AN:

86258

European-Finnish (FIN)

AF:

0.00449

AC:

240

AN:

53420

Middle Eastern (MID)

AF:

0.00763

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00920

AC:

10229

AN:

1112004

Other (OTH)

AF:

0.00838

AC:

506

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

712

1425

2137

2850

3562

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

380

760

1140

1520

1900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00636

AC:

968

AN:

152252

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

464

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

41554

American (AMR)

AF:

0.0112

AC:

171

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00518

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.00145

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00632

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00911

AC:

620

AN:

68020

Other (OTH)

AF:

0.00756

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

142

190

237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00809

Hom.:

Bravo

AF:

0.00666

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00867

EpiControl

AF:

0.0104

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.087

PromoterAI

0.0018

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over