rs10800584

Variant names:

• chr1-198711838-C-T
• rs10800584
• NM_002838.5:c.1172-1115C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002838.5(PTPRC):​c.1172-1115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,034 control chromosomes in the GnomAD database, including 13,681 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (13681 hom., cov: 32)
• Consequence: PTPRC NM_002838.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 7 publications found

Genes affected

PTPRC (HGNC:9666): (protein tyrosine phosphatase receptor type C) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitosis, and oncogenic transformation. This PTP contains an extracellular domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus is classified as a receptor type PTP. This PTP has been shown to be an essential regulator of T- and B-cell antigen receptor signaling. It functions through either direct interaction with components of the antigen receptor complexes, or by activating various Src family kinases required for the antigen receptor signaling. This PTP also suppresses JAK kinases, and thus functions as a regulator of cytokine receptor signaling. Alternatively spliced transcripts variants of this gene, which encode distinct isoforms, have been reported. [provided by RefSeq, Jun 2012]

PTPRC Gene-Disease associations (from GenCC):

• immunodeficiency 104

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• T-B+ severe combined immunodeficiency due to CD45 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002838.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRC	NM_002838.5	MANE Select	c.1172-1115C>T		intron	N/A	NP_002829.3
	PTPRC	NM_080921.4		c.689-1115C>T		intron	N/A	NP_563578.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRC	ENST00000442510.8	TSL:1 MANE Select	c.1172-1115C>T		intron	N/A	ENSP00000411355.3
	PTPRC	ENST00000348564.12	TSL:1	c.689-1115C>T		intron	N/A	ENSP00000306782.7
	PTPRC	ENST00000530727.5	TSL:1	c.830-1115C>T		intron	N/A	ENSP00000433536.2

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61458 AN: 151916 Hom.: 13638 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.373

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.405 AC: 61552 AN: 152034 Hom.: 13681 Cov.: 32 AF XY: 0.406 AC XY: 30175 AN XY: 74292

African (AFR) AF: 0.591 AC: 24492 AN: 41462

American (AMR) AF: 0.437 AC: 6672 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1199 AN: 3470

East Asian (EAS) AF: 0.390 AC: 2019 AN: 5172

South Asian (SAS) AF: 0.383 AC: 1846 AN: 4820

European-Finnish (FIN) AF: 0.318 AC: 3354 AN: 10548

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20904 AN: 67974

Other (OTH) AF: 0.372 AC: 784 AN: 2108

Alfa AF: 0.365 Hom.: 1364

Bravo AF: 0.424

Asia WGS AF: 0.421 AC: 1462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.034
DANN	Benign	0.16
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs10800584; hg19: chr1-198680967;