1-113829710-TAA-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The ENST00000359785.10(PTPN22):c.2135-5_2135-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,210,494 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 0)
  • Exomes 𝑓: 0.024 (0 hom.)
• 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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-113829710-TAA-T is Benign according to our data. Variant chr1-113829710-TAA-T is described in ClinVar as [Benign]. Clinvar id is 775137.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0243 (25843/1063444) while in subpopulation SAS AF= 0.0462 (2775/60122). AF 95% confidence interval is 0.0447. There are 0 homozygotes in gnomad4_exome. There are 13188 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN22	NM_015967.8	c.2135-5_2135-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000359785.10
PTPN22	XM_047417630.1	c.1985-5_1985-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
AP4B1-AS1	NR_125965.1	n.414+14249_414+14250del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN22	ENST00000359785.10	c.2135-5_2135-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_015967.8	P1
	ENST00000664434.1	n.419-2041_419-2040del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000456 AC: 67 AN: 146968 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000298

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000750

Gnomad ASJ AF: 0.000583

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00186

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000331

Gnomad OTH AF: 0.00148

GnomAD4 exome AF: 0.0243 AC: 25843 AN: 1063444 Hom.: 0 AF XY: 0.0247 AC XY: 13188 AN XY: 533856

Gnomad4 AFR exome AF: 0.0334

Gnomad4 AMR exome AF: 0.0141

Gnomad4 ASJ exome AF: 0.0294

Gnomad4 EAS exome AF: 0.00283

Gnomad4 SAS exome AF: 0.0462

Gnomad4 FIN exome AF: 0.0167

Gnomad4 NFE exome AF: 0.0240

Gnomad4 OTH exome AF: 0.0237

GnomAD4 genome AF: 0.000456 AC: 67 AN: 147050 Hom.: 0 Cov.: 0 AF XY: 0.000434 AC XY: 31 AN XY: 71478

Gnomad4 AFR AF: 0.000297

Gnomad4 AMR AF: 0.000750

Gnomad4 ASJ AF: 0.000583

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00186

Gnomad4 NFE AF: 0.000331

Gnomad4 OTH AF: 0.00146

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

Jun 28, 2017

- -

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;