chr19-5208305-G-T

Position:

• chr19-5208305-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002850.4(PTPRS):​c.5574C>A​(p.Asp1858Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTPRS NM_002850.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42

Genes affected

PTPRS (HGNC:9681): (protein tyrosine phosphatase receptor type S) 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 contains an extracellular region, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region of this protein is composed of multiple Ig-like and fibronectin type III-like domains. Studies of the similar gene in mice suggested that this PTP may be involved in cell-cell interaction, primary axonogenesis, and axon guidance during embryogenesis. This PTP has been also implicated in the molecular control of adult nerve repair. Four alternatively spliced transcript variants, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3164229).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.5574C>A	p.Asp1858Glu	missense_variant	36/38	ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.5574C>A	p.Asp1858Glu	missense_variant	36/38	5	NM_002850.4	ENSP00000262963	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Oct 04, 2022

The c.5574C>A (p.D1858E) alteration is located in exon 36 (coding exon 35) of the PTPRS gene. This alteration results from a C to A substitution at nucleotide position 5574, causing the aspartic acid (D) at amino acid position 1858 to be replaced by a glutamic acid (E). 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	0.94
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.63	D;.;.;.;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.033
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.32	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.90	D
REVEL	Benign	0.15
Sift4G	Benign	0.11	T;T;T;T;T
Polyphen		1.0	D;P;P;.;.
Vest4		0.52
MutPred		0.54		Gain of disorder (P = 0.1358);.;.;.;.;
MVP		0.36
ClinPred		0.94	D
GERP RS		2.9
Varity_R		0.49
gMVP		0.60

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: chr19-5208316;