1-29259505-G-A

Variant names:

• chr1-29259505-G-A
• NM_133178.4:c.616G>A

Variant summary

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

The NM_133178.4(PTPRU):​c.616G>A​(p.Ala206Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,764 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A206S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PTPRU NM_133178.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.94

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 rank	MANE	Protein	UniProt
PTPRU	NM_133178.4	c.616G>A	p.Ala206Thr	missense_variant	Exon 5 of 30	ENST00000373779.8	NP_573439.2
PTPRU	NM_005704.5	c.616G>A	p.Ala206Thr	missense_variant	Exon 5 of 31		NP_005695.3
PTPRU	NM_133177.4	c.616G>A	p.Ala206Thr	missense_variant	Exon 5 of 31		NP_573438.3
PTPRU	NM_001195001.2	c.616G>A	p.Ala206Thr	missense_variant	Exon 5 of 30		NP_001181930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRU	ENST00000373779.8	c.616G>A	p.Ala206Thr	missense_variant	Exon 5 of 30	1	NM_133178.4	ENSP00000362884.3
PTPRU	ENST00000345512.7	c.616G>A	p.Ala206Thr	missense_variant	Exon 5 of 31	1		ENSP00000334941.5
PTPRU	ENST00000460170.2	c.616G>A	p.Ala206Thr	missense_variant	Exon 5 of 31	1		ENSP00000432906.1
PTPRU	ENST00000428026.6	c.616G>A	p.Ala206Thr	missense_variant	Exon 5 of 30	1		ENSP00000392332.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459764 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 725972

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: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.0082	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;.;.;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	1.0	D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.6	M;M;M;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.7	D;D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		0.087	B;B;B;D
Vest4		0.92
MutPred		0.29		Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);
MVP		0.52
MPC		1.4
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.78

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: chr1-29586017; COSMIC: COSV100113592; COSMIC: COSV100113592;