dbSNP rs34639107: PTPN22:c.*52T>A (chr1-113819496-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000420377.6(PTPN22):c.*52T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,035,384 control chromosomes in the GnomAD database, including 215 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 0.023 ( 50 hom., cov: 32)

Exomes 𝑓: 0.016 ( 165 hom. )

Consequence

PTPN22
ENST00000420377.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.382

Publications

2 publications found

Variant links:

Genes affected

PTPN22 (HGNC:9652): (protein tyrosine phosphatase non-receptor type 22) This gene encodes of member of the non-receptor class 4 subfamily of the protein-tyrosine phosphatase family. The encoded protein is a lymphoid-specific intracellular phosphatase that associates with the molecular adapter protein CBL and may be involved in regulating CBL function in the T-cell receptor signaling pathway. Mutations in this gene may be associated with a range of autoimmune disorders including Type 1 Diabetes, rheumatoid arthritis, systemic lupus erythematosus and Graves' disease. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Mar 2009]

PTPN22 links:

AP4B1-AS1 (HGNC:44114): (AP4B1 antisense RNA 1)

AP4B1-AS1 links:

Genome browser will be placed here

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=-0.87).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0229 (3495/152330) while in subpopulation AFR AF = 0.0402 (1672/41570). AF 95% confidence interval is 0.0386. There are 50 homozygotes in GnomAd4. There are 1677 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 50 Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8 link	c.2359+81T>A		intron_variant	Intron 20 of 20	ENST00000359785.10	NP_057051.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10 link	c.2359+81T>A		intron_variant	Intron 20 of 20	1	NM_015967.8	ENSP00000352833.5

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3496

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0403

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0173

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.00269

Gnomad SAS

AF:

0.00724

Gnomad FIN

AF:

0.0277

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0158

Gnomad OTH

AF:

0.0320

GnomAD4 exome

AF:

0.0159

AC:

14044

AN:

883054

Hom.:

165

Cov.:

AF XY:

0.0155

AC XY:

6977

AN XY:

449422

show subpopulations

African (AFR)

AF:

0.0400

AC:

821

AN:

20500

American (AMR)

AF:

0.0145

AC:

407

AN:

27984

Ashkenazi Jewish (ASJ)

AF:

0.0183

AC:

352

AN:

19220

East Asian (EAS)

AF:

0.000843

AC:

AN:

34396

South Asian (SAS)

AF:

0.00725

AC:

397

AN:

54744

European-Finnish (FIN)

AF:

0.0262

AC:

1127

AN:

43090

Middle Eastern (MID)

AF:

0.0213

AC:

AN:

3518

European-Non Finnish (NFE)

AF:

0.0157

AC:

10056

AN:

640116

Other (OTH)

AF:

0.0198

AC:

780

AN:

39486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

644

1288

1932

2576

3220

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.0229

AC:

3495

AN:

152330

Hom.:

Cov.:

AF XY:

0.0225

AC XY:

1677

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0402

AC:

1672

AN:

41570

American (AMR)

AF:

0.0173

AC:

264

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0193

AC:

AN:

3470

East Asian (EAS)

AF:

0.00270

AC:

AN:

5192

South Asian (SAS)

AF:

0.00704

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0277

AC:

294

AN:

10616

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0158

AC:

1076

AN:

68024

Other (OTH)

AF:

0.0317

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

179

358

537

716

895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0220

Hom.:

Bravo

AF:

0.0227

Asia WGS

AF:

0.0190

AC:

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

0.38

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over