Variant chr12-6951726-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002831.6(PTPN6):c.126C>T(p.Ser42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,612,354 control chromosomes in the GnomAD database, including 227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 109 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 118 hom. )

Consequence

PTPN6
NM_002831.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.03

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 12-6951726-C-T is Benign according to our data. Variant chr12-6951726-C-T is described in ClinVar as [Benign]. Clinvar id is 776690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN6	NM_002831.6 linkuse as main transcript	c.126C>T	p.Ser42=	synonymous_variant	2/16	ENST00000318974.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN6	ENST00000318974.14 linkuse as main transcript	c.126C>T	p.Ser42=	synonymous_variant	2/16	1	NM_002831.6	P1	P29350-1

Frequencies

GnomAD3 genomes

AF:

0.0211

AC:

3205

AN:

152068

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00935

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00564

AC:

1398

AN:

247942

Hom.:

AF XY:

0.00416

AC XY:

561

AN XY:

134730

show subpopulations

Gnomad AFR exome

AF:

0.0760

Gnomad AMR exome

AF:

0.00388

Gnomad ASJ exome

AF:

0.00299

Gnomad EAS exome

AF:

0.000445

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000328

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00227

AC:

3318

AN:

1460168

Hom.:

118

Cov.:

AF XY:

0.00191

AC XY:

1391

AN XY:

726404

show subpopulations

Gnomad4 AFR exome

AF:

0.0771

Gnomad4 AMR exome

AF:

0.00443

Gnomad4 ASJ exome

AF:

0.00302

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000136

Gnomad4 OTH exome

AF:

0.00455

GnomAD4 genome

AF:

0.0211

AC:

3212

AN:

152186

Hom.:

109

Cov.:

AF XY:

0.0201

AC XY:

1495

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0727

Gnomad4 AMR

AF:

0.00928

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00406

Hom.:

Bravo

AF:

0.0254

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.8

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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