1-29259504-C-T

Variant names:

• chr1-29259504-C-T
• rs370586274
• NM_133178.4:c.615C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_133178.4(PTPRU):​c.615C>T​(p.Asn205Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000617 in 1,604,902 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00030 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: PTPRU NM_133178.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.61
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 1-29259504-C-T is Benign according to our data. Variant chr1-29259504-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3054887.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.61 with no splicing effect.
• BS2: High AC in GnomAd4 at 45 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133178.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRU	NM_133178.4	MANE Select	c.615C>T	p.Asn205Asn	synonymous	Exon 5 of 30	NP_573439.2	Q92729-2
	PTPRU	NM_005704.5		c.615C>T	p.Asn205Asn	synonymous	Exon 5 of 31	NP_005695.3
	PTPRU	NM_133177.4		c.615C>T	p.Asn205Asn	synonymous	Exon 5 of 31	NP_573438.3	Q92729-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRU	ENST00000373779.8	TSL:1 MANE Select	c.615C>T	p.Asn205Asn	synonymous	Exon 5 of 30	ENSP00000362884.3	Q92729-2
	PTPRU	ENST00000345512.7	TSL:1	c.615C>T	p.Asn205Asn	synonymous	Exon 5 of 31	ENSP00000334941.5	Q92729-1
	PTPRU	ENST00000460170.2	TSL:1	c.615C>T	p.Asn205Asn	synonymous	Exon 5 of 31	ENSP00000432906.1	Q92729-4

Frequencies

GnomAD3 genomes AF: 0.000298 AC: 45 AN: 151020 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.0421

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000886

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000404 AC: 10 AN: 247468 AF XY: 0.0000520

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000899

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000371 AC: 54 AN: 1453882 Hom.: 0 Cov.: 34 AF XY: 0.0000470 AC XY: 34 AN XY: 723062

African (AFR) AF: 0.00 AC: 0 AN: 33282

American (AMR) AF: 0.0000225 AC: 1 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25812

East Asian (EAS) AF: 0.00 AC: 0 AN: 39316

South Asian (SAS) AF: 0.00 AC: 0 AN: 86090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5648

European-Non Finnish (NFE) AF: 0.0000479 AC: 53 AN: 1107182

Other (OTH) AF: 0.00 AC: 0 AN: 59854

GnomAD4 genome AF: 0.000298 AC: 45 AN: 151020 Hom.: 1 Cov.: 32 AF XY: 0.000230 AC XY: 17 AN XY: 73788

African (AFR) AF: 0.0000242 AC: 1 AN: 41290

American (AMR) AF: 0.00 AC: 0 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 5044

South Asian (SAS) AF: 0.00 AC: 0 AN: 4716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000886 AC: 6 AN: 67686

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.0000279 Hom.: 0

Bravo AF: 0.000363

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PTPRU-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	4.1
DANN	Benign	0.96
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs370586274; hg19: chr1-29586016; COSMIC: COSV60524409; COSMIC: COSV60524409;