1-29255394-G-C

Position:

• chr1-29255394-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_133178.4(PTPRU):​c.193G>C​(p.Asp65His) variant causes a missense change. 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: 32)
• Consequence: PTPRU NM_133178.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.19

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.791

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRU	NM_133178.4	c.193G>C	p.Asp65His	missense_variant	2/30	ENST00000373779.8
PTPRU	NM_005704.5	c.193G>C	p.Asp65His	missense_variant	2/31
PTPRU	NM_133177.4	c.193G>C	p.Asp65His	missense_variant	2/31
PTPRU	NM_001195001.2	c.193G>C	p.Asp65His	missense_variant	2/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRU	ENST00000373779.8	c.193G>C	p.Asp65His	missense_variant	2/30	1	NM_133178.4	A1
PTPRU	ENST00000345512.7	c.193G>C	p.Asp65His	missense_variant	2/31	1		A1
PTPRU	ENST00000460170.2	c.193G>C	p.Asp65His	missense_variant	2/31	1		A1
PTPRU	ENST00000428026.6	c.193G>C	p.Asp65His	missense_variant	2/30	1		P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.193G>C (p.D65H) alteration is located in exon 2 (coding exon 2) of the PTPRU gene. This alteration results from a G to C substitution at nucleotide position 193, causing the aspartic acid (D) at amino acid position 65 to be replaced by a histidine (H). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;.;.;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.79	D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.0	M;M;M;M
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.25
Sift	Benign	0.12	T;T;T;T
Sift4G	Uncertain	0.016	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.76
MutPred		0.66		Gain of methylation at R61 (P = 0.0854);Gain of methylation at R61 (P = 0.0854);Gain of methylation at R61 (P = 0.0854);Gain of methylation at R61 (P = 0.0854);
MVP		0.31
MPC		0.96
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.38
gMVP		0.68

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: chr1-29581906;