Genetic Variant PTPN5:p.Gly520Ser (chr11-18729499-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006906.2(PTPN5):c.1558G>A(p.Gly520Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000712 in 1,601,852 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

PTPN5
NM_006906.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.55

Publications

0 publications found

Variant links:

Genes affected

PTPN5 (HGNC:9657): (protein tyrosine phosphatase non-receptor type 5) Enables phosphotyrosine residue binding activity. Predicted to be involved in peptidyl-tyrosine dephosphorylation. Predicted to act upstream of or within protein dephosphorylation. Predicted to be located in nucleoplasm. Predicted to be integral component of membrane. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

PTPN5 links:

IGSF22-AS1 (HGNC:55511): (IGSF22 antisense RNA 1)

IGSF22-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006906.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPN5	NM_006906.2	MANE Select	c.1558G>A	p.Gly520Ser	missense	Exon 14 of 15	NP_008837.1	P54829-1
PTPN5	NM_032781.4		c.1558G>A	p.Gly520Ser	missense	Exon 14 of 15	NP_116170.3
PTPN5	NM_001278238.2		c.1486G>A	p.Gly496Ser	missense	Exon 13 of 14	NP_001265167.1	P54829-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPN5	ENST00000358540.7	TSL:1 MANE Select	c.1558G>A	p.Gly520Ser	missense	Exon 14 of 15	ENSP00000351342.2	P54829-1
PTPN5	ENST00000396168.1	TSL:1	c.1486G>A	p.Gly496Ser	missense	Exon 13 of 14	ENSP00000379471.1	P54829-3
PTPN5	ENST00000935333.1		c.1633G>A	p.Gly545Ser	missense	Exon 15 of 16	ENSP00000605392.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000146

AC:

AN:

245932

AF XY:

0.000224

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000745

AC:

108

AN:

1449538

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

721844

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33368

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00120

AC:

103

AN:

86124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5204

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1106966

Other (OTH)

AF:

0.0000499

AC:

AN:

60112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.0000394

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41570

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00124

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.000107

AC:

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

0.21

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.55

MetaSVM

Uncertain

0.42

MutationAssessor

Benign

2.0

PhyloP100

7.5

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-4.1

REVEL

Pathogenic

0.79

Sift

Benign

0.054

Sift4G

Benign

0.13

Polyphen

0.90

Vest4

0.80

MutPred

0.60

Loss of catalytic residue at V521 (P = 0.1241)

MVP

0.93

MPC

1.0

ClinPred

0.23

GERP RS

4.3

Varity_R

0.57

gMVP

0.57

Mutation Taster

=13/87

disease causing

(source)

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

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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