1-29255307-G-A

Position:

• chr1-29255307-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133178.4(PTPRU):​c.106G>A​(p.Ala36Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PTPRU NM_133178.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.79

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=0.07769072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRU	NM_133178.4	c.106G>A	p.Ala36Thr	missense_variant	2/30	ENST00000373779.8	NP_573439.2
PTPRU	NM_005704.5	c.106G>A	p.Ala36Thr	missense_variant	2/31		NP_005695.3
PTPRU	NM_133177.4	c.106G>A	p.Ala36Thr	missense_variant	2/31		NP_573438.3
PTPRU	NM_001195001.2	c.106G>A	p.Ala36Thr	missense_variant	2/30		NP_001181930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRU	ENST00000373779.8	c.106G>A	p.Ala36Thr	missense_variant	2/30	1	NM_133178.4	ENSP00000362884.3
PTPRU	ENST00000345512.7	c.106G>A	p.Ala36Thr	missense_variant	2/31	1		ENSP00000334941.5
PTPRU	ENST00000460170.2	c.106G>A	p.Ala36Thr	missense_variant	2/31	1		ENSP00000432906.1
PTPRU	ENST00000428026.6	c.106G>A	p.Ala36Thr	missense_variant	2/30	1		ENSP00000392332.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251140 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135800

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461726 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000671

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Sep 26, 2024

The c.106G>A (p.A36T) alteration is located in exon 2 (coding exon 2) of the PTPRU gene. This alteration results from a G to A substitution at nucleotide position 106, causing the alanine (A) at amino acid position 36 to be replaced by a threonine (T). 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	Benign	0.069
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T;.;.;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.068
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.078	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.23	N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.20	N;N;N;N
REVEL	Benign	0.050
Sift	Benign	0.39	T;T;T;T
Sift4G	Benign	0.39	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.10
MutPred		0.36		Gain of glycosylation at A36 (P = 0.0066);Gain of glycosylation at A36 (P = 0.0066);Gain of glycosylation at A36 (P = 0.0066);Gain of glycosylation at A36 (P = 0.0066);
MVP		0.24
MPC		0.24
ClinPred		0.25	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.058
gMVP		0.18

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: rs773778550; hg19: chr1-29581819;