1-113829710-TAAAA-TAAAAA

Variant names:

• chr1-113829710-T-TA
• rs57877024
• NM_015967.8:c.2135-4dupT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015967.8(PTPN22):​c.2135-4dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.016 (0 hom.)
• Consequence: PTPN22 NM_015967.8 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• Publications: 4 publications found

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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015967.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	NM_015967.8	MANE Select	c.2135-4dupT		splice_region intron	N/A	NP_057051.4
	PTPN22	NM_001308297.2		c.2063-4dupT		splice_region intron	N/A	NP_001295226.2	F5H2S8
	PTPN22	NM_001193431.3		c.2051-4dupT		splice_region intron	N/A	NP_001180360.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	ENST00000359785.10	TSL:1 MANE Select	c.2135-4_2135-3insT		splice_region intron	N/A	ENSP00000352833.5	A0A0B4J1S7
	PTPN22	ENST00000420377.6	TSL:1	c.2135-4_2135-3insT		splice_region intron	N/A	ENSP00000388229.2	E9PMT0
	PTPN22	ENST00000538253.5	TSL:1	c.2063-4_2063-3insT		splice_region intron	N/A	ENSP00000439372.2	F5H2S8

Frequencies

GnomAD3 genomes AF: 0.000109 AC: 16 AN: 147114 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000497

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.000214

Gnomad FIN AF: 0.000763

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000750

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0112 AC: 1673 AN: 149926 AF XY: 0.0107

Gnomad AFR exome AF: 0.00431

Gnomad AMR exome AF: 0.0209

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.0413

Gnomad FIN exome AF: 0.0113

Gnomad NFE exome AF: 0.00682

Gnomad OTH exome AF: 0.0117

GnomAD4 exome AF: 0.0163 AC: 17930 AN: 1098362 Hom.: 0 Cov.: 0 AF XY: 0.0159 AC XY: 8817 AN XY: 553520

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00969 AC: 226 AN: 23328

American (AMR) AF: 0.0203 AC: 581 AN: 28662

Ashkenazi Jewish (ASJ) AF: 0.0126 AC: 251 AN: 19872

East Asian (EAS) AF: 0.0412 AC: 1314 AN: 31916

South Asian (SAS) AF: 0.0104 AC: 678 AN: 65050

European-Finnish (FIN) AF: 0.0150 AC: 624 AN: 41522

Middle Eastern (MID) AF: 0.00925 AC: 38 AN: 4106

European-Non Finnish (NFE) AF: 0.0161 AC: 13517 AN: 837662

Other (OTH) AF: 0.0152 AC: 701 AN: 46244

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000109 AC: 16 AN: 147194 Hom.: 0 Cov.: 0 AF XY: 0.000112 AC XY: 8 AN XY: 71558

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000495 AC: 2 AN: 40370

American (AMR) AF: 0.00 AC: 0 AN: 14682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3434

East Asian (EAS) AF: 0.000200 AC: 1 AN: 5010

South Asian (SAS) AF: 0.000214 AC: 1 AN: 4668

European-Finnish (FIN) AF: 0.000763 AC: 7 AN: 9174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000751 AC: 5 AN: 66620

Other (OTH) AF: 0.00 AC: 0 AN: 2050

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000046698), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 684

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs57877024; hg19: chr1-114372332;