rs79141749

Variant names:

• chr1-198709705-A-G
• rs79141749
• NM_002838.5:c.1052A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002838.5(PTPRC):​c.1052A>G​(p.Asn351Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,584,974 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0090 (17 hom., cov: 32)
  • Exomes 𝑓: 0.00097 (18 hom.)
• Consequence: PTPRC NM_002838.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.754
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036854446).
• BP6: Variant 1-198709705-A-G is Benign according to our data. Variant chr1-198709705-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 378445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00898 (1368/152314) while in subpopulation AFR AF = 0.0313 (1303/41572). AF 95% confidence interval is 0.0299. There are 17 homozygotes in GnomAd4. There are 606 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRC	NM_002838.5	MANE Select	c.1052A>G	p.Asn351Ser	missense	Exon 11 of 33	NP_002829.3
	PTPRC	NM_080921.4		c.569A>G	p.Asn190Ser	missense	Exon 8 of 30	NP_563578.2	P08575-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRC	ENST00000442510.8	TSL:1 MANE Select	c.1052A>G	p.Asn351Ser	missense	Exon 11 of 33	ENSP00000411355.3	P08575-3
	PTPRC	ENST00000348564.12	TSL:1	c.569A>G	p.Asn190Ser	missense	Exon 8 of 30	ENSP00000306782.7	P08575-4
	PTPRC	ENST00000530727.5	TSL:1	c.710A>G	p.Asn237Ser	missense	Exon 9 of 18	ENSP00000433536.2	E9PKH0

Frequencies

GnomAD3 genomes AF: 0.00897 AC: 1365 AN: 152196 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00955

GnomAD2 exomes AF: 0.00254 AC: 618 AN: 243654 AF XY: 0.00170

Gnomad AFR exome AF: 0.0361

Gnomad AMR exome AF: 0.00138

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000988

Gnomad OTH exome AF: 0.00135

GnomAD4 exome AF: 0.000974 AC: 1396 AN: 1432660 Hom.: 18 Cov.: 29 AF XY: 0.000864 AC XY: 616 AN XY: 713080

African (AFR) AF: 0.0352 AC: 1148 AN: 32626

American (AMR) AF: 0.00176 AC: 76 AN: 43258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25678

East Asian (EAS) AF: 0.00 AC: 0 AN: 39274

South Asian (SAS) AF: 0.0000607 AC: 5 AN: 82372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53086

Middle Eastern (MID) AF: 0.00108 AC: 6 AN: 5548

European-Non Finnish (NFE) AF: 0.0000339 AC: 37 AN: 1091506

Other (OTH) AF: 0.00209 AC: 124 AN: 59312

GnomAD4 genome AF: 0.00898 AC: 1368 AN: 152314 Hom.: 17 Cov.: 32 AF XY: 0.00814 AC XY: 606 AN XY: 74472

African (AFR) AF: 0.0313 AC: 1303 AN: 41572

American (AMR) AF: 0.00229 AC: 35 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

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

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68008

Other (OTH) AF: 0.00945 AC: 20 AN: 2116

Alfa AF: 0.00346 Hom.: 16

Bravo AF: 0.00996

ESP6500AA AF: 0.0267 AC: 114

ESP6500EA AF: 0.000236 AC: 2

ExAC AF: 0.00310 AC: 375

Asia WGS AF: 0.00262 AC: 9 AN: 3446

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hepatitis C virus, susceptibility to;C5676890:Immunodeficiency 104 (1)
-	-	1	Immunodeficiency 104 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	PTPRC-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.0010
DANN	Benign	0.21
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.75
PrimateAI	Benign	0.27	T
REVEL	Benign	0.0080
Sift4G	Benign	0.79	T
Vest4		0.041
MVP		0.30
MPC		0.13
ClinPred		0.0099	T
GERP RS		-1.4
Varity_R		0.045
gMVP		0.21
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs79141749; hg19: chr1-198678834;