1-198638984-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The ENST00000348564.11(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 ENST00000348564.11 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.97

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRC	XM_047426381.1	c.-44+198C>T		intron_variant
PTPRC	XM_047426398.1	c.-44+198C>T		intron_variant
PTPRC	XM_047426409.1	c.-44+198C>T		intron_variant
PTPRC	XM_047426415.1	c.-44+198C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRC	ENST00000348564.11	c.-197C>T		5_prime_UTR_variant	1/30	1		P2
PTPRC	ENST00000367379.6	c.-43-242C>T		intron_variant		5
PTPRC	ENST00000643513.1	c.-44+198C>T		intron_variant
PTPRC	ENST00000530727.5			upstream_gene_variant		1

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

Gnomad4 AFR exome AF: 0.0123

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000405

Gnomad4 OTH exome AF: 0.000985

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

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.00315

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00285

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

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
Cadd	Benign	21
Dann	Benign	0.97

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs575470980; hg19: chr1-198608114;