ENST00000413409.6:c.*36G>A

Variant names:

• chr1-198694217-G-A
• rs78958674
• ENST00000413409.6:c.*36G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000413409.6(PTPRC):​c.*36G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 1,395,476 control chromosomes in the GnomAD database, including 2,855 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (275 hom., cov: 31)
  • Exomes 𝑓: 0.062 (2580 hom.)
• Consequence: PTPRC ENST00000413409.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.508
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-198694217-G-A is Benign according to our data. Variant chr1-198694217-G-A is described in ClinVar as [Benign]. Clinvar id is 1277649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRC	NM_002838.5	c.100+1844G>A		intron_variant	Intron 3 of 32	ENST00000442510.8	NP_002829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRC	ENST00000442510.8	c.100+1844G>A		intron_variant	Intron 3 of 32	1	NM_002838.5	ENSP00000411355.3

Frequencies

GnomAD3 genomes AF: 0.0463 AC: 7020 AN: 151628 Hom.: 275 Cov.: 31

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0224

Gnomad ASJ AF: 0.0260

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0695

Gnomad OTH AF: 0.0359

GnomAD2 exomes AF: 0.0534 AC: 2798 AN: 52352 AF XY: 0.0554

Gnomad AFR exome AF: 0.0111

Gnomad AMR exome AF: 0.0178

Gnomad ASJ exome AF: 0.0263

Gnomad EAS exome AF: 0.000633

Gnomad FIN exome AF: 0.0938

Gnomad NFE exome AF: 0.0642

Gnomad OTH exome AF: 0.0374

GnomAD4 exome AF: 0.0616 AC: 76607 AN: 1243730 Hom.: 2580 Cov.: 21 AF XY: 0.0612 AC XY: 37068 AN XY: 605920

African (AFR) AF: 0.00894 AC: 226 AN: 25282

American (AMR) AF: 0.0176 AC: 319 AN: 18132

Ashkenazi Jewish (ASJ) AF: 0.0303 AC: 563 AN: 18590

East Asian (EAS) AF: 0.000310 AC: 9 AN: 29064

South Asian (SAS) AF: 0.0366 AC: 2168 AN: 59182

European-Finnish (FIN) AF: 0.0955 AC: 4208 AN: 44052

Middle Eastern (MID) AF: 0.0240 AC: 85 AN: 3540

European-Non Finnish (NFE) AF: 0.0668 AC: 66519 AN: 995082

Other (OTH) AF: 0.0494 AC: 2510 AN: 50806

GnomAD4 genome AF: 0.0462 AC: 7016 AN: 151746 Hom.: 275 Cov.: 31 AF XY: 0.0463 AC XY: 3428 AN XY: 74108

African (AFR) AF: 0.0104 AC: 430 AN: 41386

American (AMR) AF: 0.0224 AC: 340 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.0260 AC: 90 AN: 3468

East Asian (EAS) AF: 0.000390 AC: 2 AN: 5126

South Asian (SAS) AF: 0.0337 AC: 162 AN: 4814

European-Finnish (FIN) AF: 0.0982 AC: 1032 AN: 10512

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0695 AC: 4719 AN: 67940

Other (OTH) AF: 0.0355 AC: 75 AN: 2112

Alfa AF: 0.0564 Hom.: 73

Bravo AF: 0.0376

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 06, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.51
DANN	Benign	0.72
PhyloP100		-0.51
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: rs78958674; hg19: chr1-198663346;