rs34639107

chr1-113819496-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382

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 -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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN22	NM_015967.8	c.2359+81T>A		intron_variant		ENST00000359785.10
PTPN22	XM_047417630.1	c.2209+81T>A		intron_variant
AP4B1-AS1	NR_125965.1	n.414+4024A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN22	ENST00000359785.10	c.2359+81T>A		intron_variant		1	NM_015967.8	P1
	ENST00000664434.1	n.418+4024A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 3496 AN: 152212 Hom.: 50 Cov.: 32

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.: 11 AF XY: 0.0155 AC XY: 6977 AN XY: 449422

Gnomad4 AFR exome AF: 0.0400

Gnomad4 AMR exome AF: 0.0145

Gnomad4 ASJ exome AF: 0.0183

Gnomad4 EAS exome AF: 0.000843

Gnomad4 SAS exome AF: 0.00725

Gnomad4 FIN exome AF: 0.0262

Gnomad4 NFE exome AF: 0.0157

Gnomad4 OTH exome AF: 0.0198

GnomAD4 genome AF: 0.0229 AC: 3495 AN: 152330 Hom.: 50 Cov.: 32 AF XY: 0.0225 AC XY: 1677 AN XY: 74484

Gnomad4 AFR AF: 0.0402

Gnomad4 AMR AF: 0.0173

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.00704

Gnomad4 FIN AF: 0.0277

Gnomad4 NFE AF: 0.0158

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0220 Hom.: 2

Bravo AF: 0.0227

Asia WGS AF: 0.0190 AC: 65 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	11
Dann	Benign	0.70

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: rs34639107; hg19: chr1-114362118;