rs370586274

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-29259504-C-G
• chr1-29259504-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_133178.4(PTPRU):​c.615C>G​(p.Asn205Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,882 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N205N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PTPRU NM_133178.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 2 ACMG points.

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

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>G	p.Asn205Lys	missense	Exon 5 of 30	NP_573439.2	Q92729-2
	PTPRU	NM_005704.5		c.615C>G	p.Asn205Lys	missense	Exon 5 of 31	NP_005695.3
	PTPRU	NM_133177.4		c.615C>G	p.Asn205Lys	missense	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>G	p.Asn205Lys	missense	Exon 5 of 30	ENSP00000362884.3	Q92729-2
	PTPRU	ENST00000345512.7	TSL:1	c.615C>G	p.Asn205Lys	missense	Exon 5 of 31	ENSP00000334941.5	Q92729-1
	PTPRU	ENST00000460170.2	TSL:1	c.615C>G	p.Asn205Lys	missense	Exon 5 of 31	ENSP00000432906.1	Q92729-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247468 AF XY: 0.00

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: 0.00000899

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453882 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 723062

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

American (AMR) AF: 0.00 AC: 0 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: 9.03e-7 AC: 1 AN: 1107182

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.22	N
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-1.6
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.14
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.030	D
Polyphen		0.44	B
Vest4		0.94
MutPred		0.44		Gain of ubiquitination at N205 (P = 0.0219)
MVP		0.26
MPC		1.4
ClinPred		0.88	D
GERP RS		-4.5
Varity_R		0.24
gMVP		0.70
Mutation Taster		=24/76	disease causing

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

Other links and lift over

dbSNP: rs370586274; hg19: chr1-29586016;