chr1-113834946-A-A

Position:

• chr1-113834946-A-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_015967.8(PTPN22):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPN22 NM_015967.8 exon_region
• Clinical Significance: Benign criteria provided, single submitter B:2 O:1
• Conservation: PhyloP100: -0.144

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-113834946-A-A is Benign according to our data. Variant chr1-113834946-A-A is described in ClinVar as [Benign]. Clinvar id is 8909.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.		exon_region	14/21		NP_057051.4
PTPN22	NM_001308297.1	c.		exon_region	13/20		NP_001295226.2
PTPN22	NM_001193431.2	c.		exon_region	14/21		NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.		exon_region	14/21	1		ENSP00000352833.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 17, 2018

- -

Diabetes mellitus, insulin-dependent, susceptibility to Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Aug 14, 2011

- -

chronic fatigue syndrome with infection-triggered onset Other:1

risk factor, no assertion criteria provided

case-control

Institute for Medical Immunology, Charité - Universitätsmedizin Berlin

Feb 10, 2020

A allele is associated with chronic fatigue syndrome with infection-triggered onset (OR 1.63 [CI 1.04-2.55], p = 0,016) -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-114377568;