rs147233796

Variant names:

• chr1-113830002-G-A
• rs147233796
• ENST00000359785.10:c.2081C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-113830002-G-A
• chr1-113830002-G-C
• chr1-113830002-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000359785.10(PTPN22):​c.2081C>T​(p.Pro694Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,454,524 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P694Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PTPN22 ENST00000359785.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.63
• Publications: 0 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 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.2081C>T	p.Pro694Leu	missense_variant	Exon 17 of 21		NP_057051.4
PTPN22	NM_001308297.2	c.2009C>T	p.Pro670Leu	missense_variant	Exon 16 of 20		NP_001295226.2
PTPN22	NM_001193431.3	c.1997C>T	p.Pro666Leu	missense_variant	Exon 17 of 21		NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.2081C>T	p.Pro694Leu	missense_variant	Exon 17 of 21	1		ENSP00000352833.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250642 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000581

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1454524 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724022

African (AFR) AF: 0.00 AC: 0 AN: 33248

American (AMR) AF: 0.0000448 AC: 2 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39602

South Asian (SAS) AF: 0.00 AC: 0 AN: 86008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105686

Other (OTH) AF: 0.00 AC: 0 AN: 60136

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	.;.;T;.;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	D;D;D;D;T
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.57	D;D;D;D;D
MetaSVM	Uncertain	-0.073	T
PhyloP100		5.6
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-6.5	D;.;D;D;D
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;.;D;D;D
Sift4G	Uncertain	0.013	D;D;D;D;D
Polyphen		1.0	.;.;.;D;.
Vest4		0.56
MVP		0.85
MPC		0.43
ClinPred		1.0	D
GERP RS		5.1
gMVP		0.25
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs147233796; hg19: chr1-114372624;