1-198752665-C-T

Variant names:

• chr1-198752665-C-T
• rs61757805
• NM_002838.5:c.3402C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_002838.5(PTPRC):​c.3402C>T​(p.Pro1134Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,612,734 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P1134P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0024 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (74 hom.)
• Consequence: PTPRC NM_002838.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0720
• 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]

MIR181A1HG (HGNC:48659): (MIR181A1 host gene)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 1-198752665-C-T is Benign according to our data. Variant chr1-198752665-C-T is described in ClinVar as Benign. ClinVar VariationId is 138846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00244 (371/152112) while in subpopulation AMR AF = 0.0199 (303/15260). AF 95% confidence interval is 0.018. There are 4 homozygotes in GnomAd4. There are 189 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.3402C>T	p.Pro1134Pro	synonymous	Exon 31 of 33	NP_002829.3
	PTPRC	NM_080921.4		c.2919C>T	p.Pro973Pro	synonymous	Exon 28 of 30	NP_563578.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRC	ENST00000442510.8	TSL:1 MANE Select	c.3402C>T	p.Pro1134Pro	synonymous	Exon 31 of 33	ENSP00000411355.3
	PTPRC	ENST00000348564.12	TSL:1	c.2919C>T	p.Pro973Pro	synonymous	Exon 28 of 30	ENSP00000306782.7
	PTPRC	ENST00000697631.1		c.3117C>T	p.Pro1039Pro	synonymous	Exon 29 of 31	ENSP00000513363.1

Frequencies

GnomAD3 genomes AF: 0.00242 AC: 368 AN: 151994 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00330

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00787 AC: 1968 AN: 250218 AF XY: 0.00561

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.0538

Gnomad ASJ exome AF: 0.00249

Gnomad EAS exome AF: 0.00104

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.00642

GnomAD4 exome AF: 0.00175 AC: 2551 AN: 1460622 Hom.: 74 Cov.: 31 AF XY: 0.00143 AC XY: 1041 AN XY: 726650

African (AFR) AF: 0.000419 AC: 14 AN: 33420

American (AMR) AF: 0.0483 AC: 2153 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00195 AC: 51 AN: 26102

East Asian (EAS) AF: 0.00420 AC: 166 AN: 39570

South Asian (SAS) AF: 0.000661 AC: 57 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.0000306 AC: 34 AN: 1111266

Other (OTH) AF: 0.00124 AC: 75 AN: 60296

GnomAD4 genome AF: 0.00244 AC: 371 AN: 152112 Hom.: 4 Cov.: 32 AF XY: 0.00254 AC XY: 189 AN XY: 74332

African (AFR) AF: 0.000891 AC: 37 AN: 41538

American (AMR) AF: 0.0199 AC: 303 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3468

East Asian (EAS) AF: 0.00331 AC: 17 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67954

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00128 Hom.: 0

Bravo AF: 0.00510

Asia WGS AF: 0.00404 AC: 14 AN: 3476

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 28, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Immunodeficiency 105 Benign:1

Aug 07, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Immunodeficiency 104 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	14
DANN	Benign	0.40
PhyloP100		0.072
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.28		Position offset: 25

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

Other links and lift over

dbSNP: rs61757805; hg19: chr1-198721794;