1-198663227-C-T

Variant names:

• chr1-198663227-C-T
• rs1998843
• NM_002838.5:c.73+23886C>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.73+23886C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,054 control chromosomes in the GnomAD database, including 10,044 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 0.35 (10044 hom., cov: 32)
• Consequence: PTPRC NM_002838.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415
• Publications: 10 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

PTPRC-AS1 (HGNC:40483):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.66 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRC	NM_002838.5	MANE Select	c.73+23886C>T		intron	N/A	NP_002829.3
	PTPRC	NM_080921.4		c.73+23886C>T		intron	N/A	NP_563578.2	P08575-4
	PTPRC	NM_001267798.2		c.73+23886C>T		intron	N/A	NP_001254727.1	M9MML4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRC	ENST00000442510.8	TSL:1 MANE Select	c.73+23886C>T		intron	N/A	ENSP00000411355.3	P08575-3
	PTPRC	ENST00000348564.12	TSL:1	c.73+23886C>T		intron	N/A	ENSP00000306782.7	P08575-4
	PTPRC	ENST00000530727.5	TSL:1	c.73+23886C>T		intron	N/A	ENSP00000433536.2	E9PKH0

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53630 AN: 151936 Hom.: 10033 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.353 AC: 53660 AN: 152054 Hom.: 10044 Cov.: 32 AF XY: 0.358 AC XY: 26638 AN XY: 74336

African (AFR) AF: 0.281 AC: 11639 AN: 41486

American (AMR) AF: 0.386 AC: 5890 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1224 AN: 3468

East Asian (EAS) AF: 0.678 AC: 3508 AN: 5172

South Asian (SAS) AF: 0.463 AC: 2234 AN: 4820

European-Finnish (FIN) AF: 0.395 AC: 4166 AN: 10560

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23682 AN: 67958

Other (OTH) AF: 0.384 AC: 808 AN: 2106

Alfa AF: 0.352 Hom.: 15293

Bravo AF: 0.349

Asia WGS AF: 0.573 AC: 1993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.68
PhyloP100		-0.41
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: rs1998843; hg19: chr1-198632356;