1-198638984-C-T

Variant names:

• chr1-198638984-C-T
• rs575470980
• ENST00000348564.12:c.-197C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The ENST00000348564.12(PTPRC):​c.-197C>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00158 in 395,272 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00050 (2 hom.)
• Consequence: PTPRC ENST00000348564.12 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.97
• Publications: 0 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=-0.25).
• BP6: Variant 1-198638984-C-T is Benign according to our data. Variant chr1-198638984-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1212714.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0033 (502/152144) while in subpopulation AFR AF = 0.0107 (446/41504). AF 95% confidence interval is 0.00992. There are 6 homozygotes in GnomAd4. There are 234 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRC	NM_002838.5	c.-197C>T		upstream_gene_variant		ENST00000442510.8	NP_002829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRC	ENST00000442510.8	c.-197C>T		upstream_gene_variant		1	NM_002838.5	ENSP00000411355.3

Frequencies

GnomAD3 genomes AF: 0.00331 AC: 503 AN: 152026 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00315

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00288

GnomAD4 exome AF: 0.000502 AC: 122 AN: 243128 Hom.: 2 Cov.: 0 AF XY: 0.000455 AC XY: 59 AN XY: 129586

African (AFR) AF: 0.0123 AC: 92 AN: 7504

American (AMR) AF: 0.00110 AC: 10 AN: 9090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7584

East Asian (EAS) AF: 0.00 AC: 0 AN: 15904

South Asian (SAS) AF: 0.00 AC: 0 AN: 27108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1070

European-Non Finnish (NFE) AF: 0.0000405 AC: 6 AN: 148080

Other (OTH) AF: 0.000985 AC: 14 AN: 14220

GnomAD4 genome AF: 0.00330 AC: 502 AN: 152144 Hom.: 6 Cov.: 32 AF XY: 0.00315 AC XY: 234 AN XY: 74400

African (AFR) AF: 0.0107 AC: 446 AN: 41504

American (AMR) AF: 0.00315 AC: 48 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67968

Other (OTH) AF: 0.00285 AC: 6 AN: 2108

Alfa AF: 0.00229 Hom.: 0

Bravo AF: 0.00393

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 06, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Benign	0.97
PhyloP100		5.0
PromoterAI		-0.42	Neutral
Mutation Taster		=94/6	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs575470980; hg19: chr1-198608114;