rs145944629

Variant names:

• chr1-198749475-G-A
• rs145944629
• NM_002838.5:c.2998G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002838.5(PTPRC):​c.2998G>A​(p.Asp1000Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000164 in 1,609,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1000E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: PTPRC NM_002838.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 5.94
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1542801).

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.2998G>A	p.Asp1000Asn	missense	Exon 28 of 33	NP_002829.3
	PTPRC	NM_080921.4		c.2515G>A	p.Asp839Asn	missense	Exon 25 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.2998G>A	p.Asp1000Asn	missense	Exon 28 of 33	ENSP00000411355.3	P08575-3
	PTPRC	ENST00000348564.12	TSL:1	c.2515G>A	p.Asp839Asn	missense	Exon 25 of 30	ENSP00000306782.7	P08575-4
	PTPRC	ENST00000697631.1		c.2713G>A	p.Asp905Asn	missense	Exon 26 of 31	ENSP00000513363.1	P08575-8

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 151838 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

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: 0.000280

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000192 AC: 48 AN: 249392 AF XY: 0.000178

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000347

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000165 AC: 241 AN: 1457232 Hom.: 0 Cov.: 31 AF XY: 0.000172 AC XY: 125 AN XY: 725156

African (AFR) AF: 0.0000300 AC: 1 AN: 33310

American (AMR) AF: 0.000202 AC: 9 AN: 44528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26018

East Asian (EAS) AF: 0.00 AC: 0 AN: 39338

South Asian (SAS) AF: 0.00 AC: 0 AN: 86166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5744

European-Non Finnish (NFE) AF: 0.000202 AC: 224 AN: 1108700

Other (OTH) AF: 0.0000832 AC: 5 AN: 60112

GnomAD4 genome AF: 0.000151 AC: 23 AN: 151838 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74126

African (AFR) AF: 0.0000242 AC: 1 AN: 41400

American (AMR) AF: 0.000197 AC: 3 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000280 AC: 19 AN: 67846

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000326 Hom.: 1

Bravo AF: 0.000181

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000255 AC: 31

EpiCase AF: 0.000382

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Immunodeficiency 104 (1)
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.58
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.2	T
PhyloP100		5.9
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.24
Sift	Benign	0.057	T
Sift4G	Benign	0.16	T
Vest4		0.29
MVP		0.48
MPC		0.68
ClinPred		0.22	T
GERP RS		5.8
Varity_R		0.15
gMVP		0.49
Mutation Taster		=56/44	polymorphism

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: rs145944629; hg19: chr1-198718604; COSMIC: COSV61406021; COSMIC: COSV61406021;