1-29258738-G-C

Variant names:

• chr1-29258738-G-C
• NM_133178.4:c.439G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_133178.4(PTPRU):​c.439G>C​(p.Glu147Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTPRU NM_133178.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.92

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRU	NM_133178.4	c.439G>C	p.Glu147Gln	missense_variant	Exon 3 of 30	ENST00000373779.8	NP_573439.2
PTPRU	NM_005704.5	c.439G>C	p.Glu147Gln	missense_variant	Exon 3 of 31		NP_005695.3
PTPRU	NM_133177.4	c.439G>C	p.Glu147Gln	missense_variant	Exon 3 of 31		NP_573438.3
PTPRU	NM_001195001.2	c.439G>C	p.Glu147Gln	missense_variant	Exon 3 of 30		NP_001181930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRU	ENST00000373779.8	c.439G>C	p.Glu147Gln	missense_variant	Exon 3 of 30	1	NM_133178.4	ENSP00000362884.3
PTPRU	ENST00000345512.7	c.439G>C	p.Glu147Gln	missense_variant	Exon 3 of 31	1		ENSP00000334941.5
PTPRU	ENST00000460170.2	c.439G>C	p.Glu147Gln	missense_variant	Exon 3 of 31	1		ENSP00000432906.1
PTPRU	ENST00000428026.6	c.439G>C	p.Glu147Gln	missense_variant	Exon 3 of 30	1		ENSP00000392332.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.439G>C (p.E147Q) alteration is located in exon 3 (coding exon 3) of the PTPRU gene. This alteration results from a G to C substitution at nucleotide position 439, causing the glutamic acid (E) at amino acid position 147 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;.;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D;D
M_CAP	Benign	0.068	D
MetaRNN	Pathogenic	0.92	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L;L;L
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Uncertain	0.37
Sift	Benign	0.047	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.81
MutPred		0.83		Gain of MoRF binding (P = 0.0423);Gain of MoRF binding (P = 0.0423);Gain of MoRF binding (P = 0.0423);Gain of MoRF binding (P = 0.0423);
MVP		0.44
MPC		0.89
ClinPred		0.94	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.62
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-29585250;