Genetic Variant NM_002831.6:c.1099G>A (chr12-6957678-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002831.6(PTPN6):c.1099G>A(p.Glu367Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000764 in 1,296,404 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

PTPN6
NM_002831.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.43

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 39 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002831.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPN6	NM_002831.6	MANE Select	c.1099G>A	p.Glu367Lys	missense	Exon 10 of 16	NP_002822.2
PTPN6	NM_080549.4		c.1099G>A	p.Glu367Lys	missense	Exon 10 of 16	NP_536859.1	P29350-4
PTPN6	NM_080548.5		c.1105G>A	p.Glu369Lys	missense	Exon 10 of 16	NP_536858.1	Q53XS4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPN6	ENST00000318974.14	TSL:1 MANE Select	c.1099G>A	p.Glu367Lys	missense	Exon 10 of 16	ENSP00000326010.9	P29350-1
PTPN6	ENST00000456013.5	TSL:1	c.1099G>A	p.Glu367Lys	missense	Exon 10 of 16	ENSP00000391592.1	P29350-4
PTPN6	ENST00000399448.5	TSL:1	c.1105G>A	p.Glu369Lys	missense	Exon 10 of 16	ENSP00000382376.1	P29350-3

Frequencies

GnomAD3 genomes

AF:

0.000274

AC:

AN:

142346

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000779

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000277

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:

0.0000309

Gnomad OTH

AF:

0.000999

GnomAD2 exomes

AF:

0.0000803

AC:

AN:

249000

AF XY:

0.0000813

show subpopulations

Gnomad AFR exome

AF:

0.000518

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1154058

Hom.:

Cov.:

AF XY:

0.0000504

AC XY:

AN XY:

575390

show subpopulations

African (AFR)

AF:

0.000913

AC:

AN:

25182

American (AMR)

AF:

0.000239

AC:

AN:

37580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16924

East Asian (EAS)

AF:

0.00

AC:

AN:

17666

South Asian (SAS)

AF:

0.0000243

AC:

AN:

82454

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4396

European-Non Finnish (NFE)

AF:

0.0000280

AC:

AN:

894072

Other (OTH)

AF:

0.0000236

AC:

AN:

42342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000274

AC:

AN:

142346

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

AN XY:

69122

show subpopulations

African (AFR)

AF:

0.000779

AC:

AN:

39788

American (AMR)

AF:

0.000277

AC:

AN:

14436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3324

East Asian (EAS)

AF:

0.00

AC:

AN:

4110

South Asian (SAS)

AF:

0.00

AC:

AN:

3866

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8864

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.0000309

AC:

AN:

64790

Other (OTH)

AF:

0.000999

AC:

AN:

2002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000250

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.000499

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000910

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.81

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.095

MetaRNN

Uncertain

0.65

MetaSVM

Uncertain

0.26

MutationAssessor

Benign

1.4

PhyloP100

6.4

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.62

Sift

Uncertain

0.010

Sift4G

Uncertain

0.037

Polyphen

0.97

Vest4

0.60

MVP

0.68

MPC

1.7

ClinPred

0.23

GERP RS

5.1

Varity_R

0.37

gMVP

0.75

Mutation Taster

=72/28

polymorphism

(source)

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

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