rs3789609

Positions:

• chr1-113855177-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015967.8(PTPN22):​c.541-128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 757,308 control chromosomes in the GnomAD database, including 29,972 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 0.22 (4521 hom., cov: 31)
  • Exomes 𝑓: 0.28 (25451 hom.)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.541-128G>A		intron_variant			NP_057051.4
PTPN22	NM_001308297.1	c.469-128G>A		intron_variant			NP_001295226.2
PTPN22	NM_001193431.2	c.541-128G>A		intron_variant			NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.541-128G>A		intron_variant		1		ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33062 AN: 152012 Hom.: 4522 Cov.: 31

Gnomad AFR AF: 0.0594

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0936

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.280 AC: 169432 AN: 605178 Hom.: 25451 AF XY: 0.286 AC XY: 89724 AN XY: 313996

Gnomad4 AFR exome AF: 0.0544

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.0861

Gnomad4 SAS exome AF: 0.380

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.276

GnomAD4 genome AF: 0.217 AC: 33068 AN: 152130 Hom.: 4521 Cov.: 31 AF XY: 0.218 AC XY: 16205 AN XY: 74374

Gnomad4 AFR AF: 0.0593

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.0936

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.246

Alfa AF: 0.247 Hom.: 902

Bravo AF: 0.207

Asia WGS AF: 0.239 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.87
DANN	Benign	0.48

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: rs3789609; hg19: chr1-114397799;