rs57877024

Variant names:

• chr1-113829710-TAAA-T
• rs57877024
• ENST00000359785.10:c.2135-6_2135-4delTTT

Your query was ambiguous. Multiple possible variants found:

• chr1-113829710-TAAA-T
• chr1-113829710-TAAA-TA
• chr1-113829710-TAAA-TAA
• chr1-113829710-TAAA-TAAAA
• chr1-113829710-TAAA-TAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015967.8(PTPN22):​c.2135-6_2135-4delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000742 in 1,266,392 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000068 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000083 (0 hom.)
• Consequence: PTPN22 NM_015967.8 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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]

ENSG00000231128 (HGNC:):

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.2135-6_2135-4delTTT		splice_region_variant, intron_variant	Intron 17 of 20		NP_057051.4
PTPN22	NM_001308297.2	c.2063-6_2063-4delTTT		splice_region_variant, intron_variant	Intron 16 of 19		NP_001295226.2
PTPN22	NM_001193431.3	c.2051-6_2051-4delTTT		splice_region_variant, intron_variant	Intron 17 of 20		NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.2135-6_2135-4delTTT		splice_region_variant, intron_variant	Intron 17 of 20	1		ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.00000680 AC: 1 AN: 147106 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000109

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000831 AC: 93 AN: 1119286 Hom.: 0 AF XY: 0.0000851 AC XY: 48 AN XY: 564082

Gnomad4 AFR exome AF: 0.000127

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000182

Gnomad4 FIN exome AF: 0.0000469

Gnomad4 NFE exome AF: 0.0000834

Gnomad4 OTH exome AF: 0.000106

GnomAD4 genome AF: 0.00000680 AC: 1 AN: 147106 Hom.: 0 Cov.: 0 AF XY: 0.0000140 AC XY: 1 AN XY: 71462

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000109

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;