rs148144154

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-29255382-C-G
• chr1-29255382-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133178.4(PTPRU):​c.181C>G​(p.Arg61Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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 0.0000066 (0 hom., cov: 32)
• Consequence: PTPRU NM_133178.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20883933).

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>G	p.Arg61Gly	missense	Exon 2 of 30	NP_573439.2	Q92729-2
	PTPRU	NM_005704.5		c.181C>G	p.Arg61Gly	missense	Exon 2 of 31	NP_005695.3
	PTPRU	NM_133177.4		c.181C>G	p.Arg61Gly	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>G	p.Arg61Gly	missense	Exon 2 of 30	ENSP00000362884.3	Q92729-2
	PTPRU	ENST00000345512.7	TSL:1	c.181C>G	p.Arg61Gly	missense	Exon 2 of 31	ENSP00000334941.5	Q92729-1
	PTPRU	ENST00000460170.2	TSL:1	c.181C>G	p.Arg61Gly	missense	Exon 2 of 31	ENSP00000432906.1	Q92729-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74346

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00 AC: 0 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: 0.000207 AC: 1 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: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.055
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.065	N
PhyloP100		4.9
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.062
Sift	Benign	0.28	T
Sift4G	Benign	0.26	T
Polyphen		0.068	B
Vest4		0.61
MutPred		0.46		Loss of methylation at R61 (P = 0.0875)
MVP		0.15
MPC		0.38
ClinPred		0.62	D
GERP RS		5.1
Varity_R		0.20
gMVP		0.27
Mutation Taster		=84/16	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;