Variant chr12-6951602-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002831.6(PTPN6):c.9-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000312 in 1,613,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

PTPN6
NM_002831.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004374

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.647

Variant links:

Genes affected

PTPN6 (HGNC:9658): (protein tyrosine phosphatase non-receptor type 6) 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. N-terminal part of this PTP contains two tandem Src homolog (SH2) domains, which act as protein phospho-tyrosine binding domains, and mediate the interaction of this PTP with its substrates. This PTP is expressed primarily in hematopoietic cells, and functions as an important regulator of multiple signaling pathways in hematopoietic cells. This PTP has been shown to interact with, and dephosphorylate a wide spectrum of phospho-proteins involved in hematopoietic cell signaling. Multiple alternatively spliced variants of this gene, which encode distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]

PTPN6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BS2

High AC in GnomAd4 at 207 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN6	NM_002831.6 linkuse as main transcript	c.9-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000318974.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN6	ENST00000318974.14 linkuse as main transcript	c.9-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002831.6	P1	P29350-1

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

208

AN:

151902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00464

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

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:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000481

AC:

120

AN:

249242

Hom.:

AF XY:

0.000384

AC XY:

AN XY:

135340

show subpopulations

Gnomad AFR exome

AF:

0.00576

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000619

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000203

AC:

297

AN:

1461766

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

143

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00559

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000540

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.00136

AC:

207

AN:

152024

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00463

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Bravo

AF:

0.00157

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Mar 30, 2021

PTPN6 NM_080549.3 exon 2 c.9-7C>T: This variant has not been reported in the literature but is present in 0.5% (127/24124) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/12-7060765-C-T?dataset=gnomad_r2_1). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is an intronic variant; splice prediction tools suggest that this variant may not affect splicing. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.2

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000044

dbscSNV1_RF

Benign

0.020

SpliceAI score (max)

0.010

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