Genetic Variant PTPN5:c.20+126A>G (chr11-18771813-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006906.2(PTPN5):c.20+126A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 791,040 control chromosomes in the GnomAD database, including 101,769 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 17086 hom., cov: 33)

Exomes 𝑓: 0.51 ( 84683 hom. )

Consequence

PTPN5
NM_006906.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.346

Publications

7 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
PTPN5	NM_006906.2	MANE Select	c.20+126A>G	intron	N/A	NP_008837.1	P54829-1
PTPN5	NM_032781.4		c.20+126A>G	intron	N/A	NP_116170.3
PTPN5	NM_001278238.2		c.-52-5930A>G	intron	N/A	NP_001265167.1	P54829-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PTPN5	ENST00000358540.7	TSL:1 MANE Select	c.20+126A>G	intron	N/A	ENSP00000351342.2	P54829-1
PTPN5	ENST00000396168.1	TSL:1	c.-52-5930A>G	intron	N/A	ENSP00000379471.1	P54829-3
PTPN5	ENST00000935333.1		c.20+126A>G	intron	N/A	ENSP00000605392.1

Frequencies

GnomAD3 genomes

AF:

0.458

AC:

69606

AN:

151948

Hom.:

17076

Cov.:

show subpopulations

Gnomad AFR

AF:

0.306

Gnomad AMI

AF:

0.473

Gnomad AMR

AF:

0.554

Gnomad ASJ

AF:

0.397

Gnomad EAS

AF:

0.874

Gnomad SAS

AF:

0.581

Gnomad FIN

AF:

0.513

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.483

Gnomad OTH

AF:

0.465

GnomAD4 exome

AF:

0.506

AC:

323478

AN:

638974

Hom.:

84683

AF XY:

0.505

AC XY:

173411

AN XY:

343310

show subpopulations

African (AFR)

AF:

0.305

AC:

4272

AN:

13988

American (AMR)

AF:

0.603

AC:

15144

AN:

25096

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

7350

AN:

18650

East Asian (EAS)

AF:

0.873

AC:

26675

AN:

30566

South Asian (SAS)

AF:

0.536

AC:

29788

AN:

55616

European-Finnish (FIN)

AF:

0.504

AC:

25823

AN:

51230

Middle Eastern (MID)

AF:

0.428

AC:

1251

AN:

2920

European-Non Finnish (NFE)

AF:

0.483

AC:

197131

AN:

408182

Other (OTH)

AF:

0.490

AC:

16044

AN:

32726

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

8053

16106

24160

32213

40266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2604

5208

7812

10416

13020

<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:

0.458

AC:

69657

AN:

152066

Hom.:

17086

Cov.:

AF XY:

0.466

AC XY:

34656

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.307

AC:

12710

AN:

41462

American (AMR)

AF:

0.555

AC:

8483

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.397

AC:

1379

AN:

3470

East Asian (EAS)

AF:

0.873

AC:

4519

AN:

5178

South Asian (SAS)

AF:

0.581

AC:

2800

AN:

4818

European-Finnish (FIN)

AF:

0.513

AC:

5418

AN:

10560

Middle Eastern (MID)

AF:

0.480

AC:

141

AN:

294

European-Non Finnish (NFE)

AF:

0.483

AC:

32797

AN:

67972

Other (OTH)

AF:

0.465

AC:

980

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1859

3718

5576

7435

9294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<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:

0.477

Hom.:

17268

Bravo

AF:

0.455

Asia WGS

AF:

0.687

AC:

2387

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.63

(source)

DANN

Benign

0.55

PhyloP100

-0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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