Variant 12-6957662-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_002831.6(PTPN6):c.1083C>T(p.Cys361=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000905 in 1,394,556 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 4 hom. )

Consequence

PTPN6
NM_002831.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.550

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 12-6957662-C-T is Benign according to our data. Variant chr12-6957662-C-T is described in ClinVar as [Benign]. Clinvar id is 777231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.55 with no splicing effect.

BS2

High AC in GnomAd4 at 461 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN6	NM_002831.6 linkuse as main transcript	c.1083C>T	p.Cys361=	synonymous_variant	10/16	ENST00000318974.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN6	ENST00000318974.14 linkuse as main transcript	c.1083C>T	p.Cys361=	synonymous_variant	10/16	1	NM_002831.6	P1	P29350-1
PTPN6	ENST00000456013.5 linkuse as main transcript	c.1083C>T	p.Cys361=	synonymous_variant	10/16	1			P29350-4
PTPN6	ENST00000399448.5 linkuse as main transcript	c.1089C>T	p.Cys363=	synonymous_variant	10/16	1			P29350-3
PTPN6	ENST00000416215.6 linkuse as main transcript	n.1491C>T		non_coding_transcript_exon_variant	9/15	2

Frequencies

GnomAD3 genomes

AF:

0.00306

AC:

459

AN:

149800

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00969

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00172

Gnomad ASJ

AF:

0.00524

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000216

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000134

Gnomad OTH

AF:

0.00337

GnomAD3 exomes

AF:

0.00138

AC:

344

AN:

248600

Hom.:

AF XY:

0.00115

AC XY:

156

AN XY:

135098

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.00238

Gnomad ASJ exome

AF:

0.00498

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000151

Gnomad OTH exome

AF:

0.00381

GnomAD4 exome

AF:

0.000644

AC:

801

AN:

1244642

Hom.:

Cov.:

AF XY:

0.000552

AC XY:

344

AN XY:

623056

show subpopulations

Gnomad4 AFR exome

AF:

0.0126

Gnomad4 AMR exome

AF:

0.00251

Gnomad4 ASJ exome

AF:

0.00664

Gnomad4 EAS exome

AF:

0.0000325

Gnomad4 SAS exome

AF:

0.0000967

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000119

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.00308

AC:

461

AN:

149914

Hom.:

Cov.:

AF XY:

0.00333

AC XY:

244

AN XY:

73278

show subpopulations

Gnomad4 AFR

AF:

0.00971

Gnomad4 AMR

AF:

0.00171

Gnomad4 ASJ

AF:

0.00524

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000216

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000134

Gnomad4 OTH

AF:

0.00334

Alfa

AF:

0.00203

Hom.:

Bravo

AF:

0.00380

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

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

-0.44

CADD

Benign

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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