chr1-29255382-C-T

Variant names:

• chr1-29255382-C-T
• rs148144154
• NM_133178.4:c.181C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_133178.4(PTPRU):​c.181C>T​(p.Arg61Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000489 in 1,614,036 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. R61Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: PTPRU NM_133178.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.92
• Publications: 4 publications found

Genes affected

PTPRU (HGNC:9683): (protein tyrosine phosphatase receptor type U) 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, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and two tandem intracellular catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP (MAM) domain, Ig-like and fibronectin type III-like repeats. This PTP was thought to play roles in cell-cell recognition and adhesion. Studies of the similar gene in mice suggested the role of this PTP in early neural development. The expression of this gene was reported to be regulated by phorbol myristate acetate (PMA) or calcium ionophore in Jurkat T lymphoma cells. Alternatively spliced transcript variants have been reported. [provided by RefSeq, Aug 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.35219023).
• BS2: High AC in GnomAd4 at 15 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133178.4. 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
	PTPRU	NM_133178.4	MANE Select	c.181C>T	p.Arg61Trp	missense	Exon 2 of 30	NP_573439.2	Q92729-2
	PTPRU	NM_005704.5		c.181C>T	p.Arg61Trp	missense	Exon 2 of 31	NP_005695.3
	PTPRU	NM_133177.4		c.181C>T	p.Arg61Trp	missense	Exon 2 of 31	NP_573438.3	Q92729-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRU	ENST00000373779.8	TSL:1 MANE Select	c.181C>T	p.Arg61Trp	missense	Exon 2 of 30	ENSP00000362884.3	Q92729-2
	PTPRU	ENST00000345512.7	TSL:1	c.181C>T	p.Arg61Trp	missense	Exon 2 of 31	ENSP00000334941.5	Q92729-1
	PTPRU	ENST00000460170.2	TSL:1	c.181C>T	p.Arg61Trp	missense	Exon 2 of 31	ENSP00000432906.1	Q92729-4

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.000132

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251336 AF XY: 0.0000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000438 AC: 64 AN: 1461832 Hom.: 0 Cov.: 30 AF XY: 0.0000468 AC XY: 34 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000157 AC: 7 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000468 AC: 52 AN: 1111990

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74346

African (AFR) AF: 0.0000724 AC: 3 AN: 41438

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68032

Other (OTH) AF: 0.000955 AC: 2 AN: 2094

Alfa AF: 0.0000964 Hom.: 1

Bravo AF: 0.000144

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.9
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.085
Sift	Benign	0.13	T
Sift4G	Benign	0.13	T
Polyphen		0.98	D
Vest4		0.61
MVP		0.15
MPC		0.70
ClinPred		0.22	T
GERP RS		5.1
Varity_R		0.19
gMVP		0.29
Mutation Taster		=81/19	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: rs148144154; hg19: chr1-29581894; COSMIC: COSV60536674; COSMIC: COSV60536674;