1-113829671-C-G

Variant names:

• chr1-113829671-C-G
• rs780598571
• ENST00000359785.10:c.2171G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000359785.10(PTPN22):​c.2171G>C​(p.Ser724Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPN22 ENST00000359785.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.153
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.110800326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.2171G>C	p.Ser724Thr	missense_variant	Exon 18 of 21		NP_057051.4
PTPN22	NM_001308297.2	c.2099G>C	p.Ser700Thr	missense_variant	Exon 17 of 20		NP_001295226.2
PTPN22	NM_001193431.3	c.2087G>C	p.Ser696Thr	missense_variant	Exon 18 of 21		NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.2171G>C	p.Ser724Thr	missense_variant	Exon 18 of 21	1		ENSP00000352833.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Aug 09, 2021

AiLife Diagnostics, AiLife Diagnostics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.91
DEOGEN2	Benign	0.028	.;.;T;.;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.70	T;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		0.15
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.5	N;.;N;N;N
REVEL	Benign	0.059
Sift	Benign	0.081	T;.;T;T;T
Sift4G	Benign	0.077	T;T;T;D;D
Polyphen		0.020	.;.;.;B;.
Vest4		0.085
MutPred		0.13		Gain of relative solvent accessibility (P = 0.0479);.;.;Gain of relative solvent accessibility (P = 0.0479);.;
MVP		0.45
MPC		0.072
ClinPred		0.040	T
GERP RS		1.8
gMVP		0.15
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs780598571; hg19: chr1-114372293;