1-29259301-A-C

Position:

• chr1-29259301-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_133178.4(PTPRU):​c.518A>C​(p.Tyr173Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PTPRU NM_133178.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.26

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRU	NM_133178.4	c.518A>C	p.Tyr173Ser	missense_variant	4/30	ENST00000373779.8	NP_573439.2
PTPRU	NM_005704.5	c.518A>C	p.Tyr173Ser	missense_variant	4/31		NP_005695.3
PTPRU	NM_133177.4	c.518A>C	p.Tyr173Ser	missense_variant	4/31		NP_573438.3
PTPRU	NM_001195001.2	c.518A>C	p.Tyr173Ser	missense_variant	4/30		NP_001181930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRU	ENST00000373779.8	c.518A>C	p.Tyr173Ser	missense_variant	4/30	1	NM_133178.4	ENSP00000362884.3
PTPRU	ENST00000345512.7	c.518A>C	p.Tyr173Ser	missense_variant	4/31	1		ENSP00000334941.5
PTPRU	ENST00000460170.2	c.518A>C	p.Tyr173Ser	missense_variant	4/31	1		ENSP00000432906.1
PTPRU	ENST00000428026.6	c.518A>C	p.Tyr173Ser	missense_variant	4/30	1		ENSP00000392332.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461828 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727218

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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 02, 2024

The c.518A>C (p.Y173S) alteration is located in exon 4 (coding exon 4) of the PTPRU gene. This alteration results from a A to C substitution at nucleotide position 518, causing the tyrosine (Y) at amino acid position 173 to be replaced by a serine (S). 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	0.66
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.25	T;.;.;.
Eigen	Benign	-0.049
Eigen_PC	Benign	0.094
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.2	M;M;M;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.7	D;D;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		0.12	B;B;B;B
Vest4		0.76
MutPred		0.58		Gain of disorder (P = 0.0021);Gain of disorder (P = 0.0021);Gain of disorder (P = 0.0021);Gain of disorder (P = 0.0021);
MVP		0.082
MPC		0.71
ClinPred		1.0	D
GERP RS		3.9
Varity_R		0.89
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-29585813;