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. Variant got 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. 13/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRU	NM_133178.4	c.181C>G	p.Arg61Gly	missense_variant	Exon 2 of 30	ENST00000373779.8	NP_573439.2
PTPRU	NM_005704.5	c.181C>G	p.Arg61Gly	missense_variant	Exon 2 of 31		NP_005695.3
PTPRU	NM_133177.4	c.181C>G	p.Arg61Gly	missense_variant	Exon 2 of 31		NP_573438.3
PTPRU	NM_001195001.2	c.181C>G	p.Arg61Gly	missense_variant	Exon 2 of 30		NP_001181930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRU	ENST00000373779.8	c.181C>G	p.Arg61Gly	missense_variant	Exon 2 of 30	1	NM_133178.4	ENSP00000362884.3
PTPRU	ENST00000345512.7	c.181C>G	p.Arg61Gly	missense_variant	Exon 2 of 31	1		ENSP00000334941.5
PTPRU	ENST00000460170.2	c.181C>G	p.Arg61Gly	missense_variant	Exon 2 of 31	1		ENSP00000432906.1
PTPRU	ENST00000428026.6	c.181C>G	p.Arg61Gly	missense_variant	Exon 2 of 30	1		ENSP00000392332.2

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

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.065	N;N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.062
Sift	Benign	0.28	T;T;T;T
Sift4G	Benign	0.26	T;T;T;T
Polyphen		0.068	B;B;B;B
Vest4		0.61
MutPred		0.46		Loss of methylation at R61 (P = 0.0875);Loss of methylation at R61 (P = 0.0875);Loss of methylation at R61 (P = 0.0875);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs148144154; hg19: chr1-29581894;