Variant chr12-6957776-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_002831.6(PTPN6):c.1197G>A(p.Pro399=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 1,614,124 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 23 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 20 hom. )

Consequence

PTPN6
NM_002831.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.31

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=-0.8).

BP6

Variant 12-6957776-G-A is Benign according to our data. Variant chr12-6957776-G-A is described in ClinVar as [Benign]. Clinvar id is 778582.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-6.31 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1795/152332) while in subpopulation AFR AF= 0.0388 (1611/41562). AF 95% confidence interval is 0.0372. There are 23 homozygotes in gnomad4. There are 871 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1795 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN6	NM_002831.6 linkuse as main transcript	c.1197G>A	p.Pro399=	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.1197G>A	p.Pro399=	synonymous_variant	10/16	1	NM_002831.6	P1	P29350-1
PTPN6	ENST00000456013.5 linkuse as main transcript	c.1197G>A	p.Pro399=	synonymous_variant	10/16	1			P29350-4
PTPN6	ENST00000399448.5 linkuse as main transcript	c.1203G>A	p.Pro401=	synonymous_variant	10/16	1			P29350-3
PTPN6	ENST00000416215.6 linkuse as main transcript	n.1605G>A		non_coding_transcript_exon_variant	9/15	2

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1791

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0388

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00569

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00352

AC:

878

AN:

249246

Hom.:

AF XY:

0.00270

AC XY:

366

AN XY:

135326

show subpopulations

Gnomad AFR exome

AF:

0.0352

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.0170

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000425

Gnomad OTH exome

AF:

0.00281

GnomAD4 exome

AF:

0.00155

AC:

2262

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

1011

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0337

Gnomad4 AMR exome

AF:

0.00324

Gnomad4 ASJ exome

AF:

0.0170

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000245

Gnomad4 OTH exome

AF:

0.00412

GnomAD4 genome

AF:

0.0118

AC:

1795

AN:

152332

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

871

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0388

Gnomad4 AMR

AF:

0.00569

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00506

Hom.:

Bravo

AF:

0.0130

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.42

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

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