1-113829710-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000359785.10(PTPN22):c.2135-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (24361 hom., cov: 0)
  • Exomes 𝑓: 0.48 (38879 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTPN22 ENST00000359785.10 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.68

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-113829710-TA-T is Benign according to our data. Variant chr1-113829710-TA-T is described in ClinVar as [Benign]. Clinvar id is 769239.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN22	NM_015967.8	c.2135-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000359785.10
PTPN22	XM_047417630.1	c.1985-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
AP4B1-AS1	NR_125965.1	n.414+14250del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN22	ENST00000359785.10	c.2135-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_015967.8	P1
	ENST00000664434.1	n.419-2040del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.570 AC: 83756 AN: 146898 Hom.: 24341 Cov.: 0

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.591

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.552

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.480 AC: 515139 AN: 1073118 Hom.: 38879 Cov.: 0 AF XY: 0.482 AC XY: 260719 AN XY: 540598

Gnomad4 AFR exome AF: 0.522

Gnomad4 AMR exome AF: 0.450

Gnomad4 ASJ exome AF: 0.496

Gnomad4 EAS exome AF: 0.348

Gnomad4 SAS exome AF: 0.512

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.481

Gnomad4 OTH exome AF: 0.485

GnomAD4 genome AF: 0.570 AC: 83817 AN: 146980 Hom.: 24361 Cov.: 0 AF XY: 0.565 AC XY: 40327 AN XY: 71428

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.549

Bravo AF: 0.558

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 30, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs57877024; hg19: chr1-114372332;