rs148478353

Variant names:

• chr19-5208324-G-A
• rs148478353
• NM_002850.4:c.5555C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002850.4(PTPRS):​c.5555C>T​(p.Ser1852Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: PTPRS NM_002850.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 7.82
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008572847).
• BP6: Variant 19-5208324-G-A is Benign according to our data. Variant chr19-5208324-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 726821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 168 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002850.4. 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
	PTPRS	NM_002850.4	MANE Select	c.5555C>T	p.Ser1852Leu	missense	Exon 36 of 38	NP_002841.3
	PTPRS	NM_001394011.1		c.5489C>T	p.Ser1830Leu	missense	Exon 32 of 34	NP_001380940.1
	PTPRS	NM_001394012.1		c.5468C>T	p.Ser1823Leu	missense	Exon 32 of 34	NP_001380941.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRS	ENST00000262963.11	TSL:5 MANE Select	c.5555C>T	p.Ser1852Leu	missense	Exon 36 of 38	ENSP00000262963.8	Q13332-1
	PTPRS	ENST00000587303.5	TSL:1	c.5555C>T	p.Ser1852Leu	missense	Exon 35 of 37	ENSP00000467537.1	Q13332-1
	PTPRS	ENST00000588012.5	TSL:1	c.5441C>T	p.Ser1814Leu	missense	Exon 30 of 32	ENSP00000465443.1	Q13332-6

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 168 AN: 152184 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00391

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.0000147

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000223 AC: 56 AN: 251086 AF XY: 0.000170

Gnomad AFR exome AF: 0.00320

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.000105 AC: 154 AN: 1461630 Hom.: 0 Cov.: 32 AF XY: 0.0000935 AC XY: 68 AN XY: 727106

African (AFR) AF: 0.00421 AC: 141 AN: 33478

American (AMR) AF: 0.0000895 AC: 4 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111868

Other (OTH) AF: 0.0000828 AC: 5 AN: 60378

GnomAD4 genome AF: 0.00110 AC: 168 AN: 152302 Hom.: 0 Cov.: 33 AF XY: 0.000953 AC XY: 71 AN XY: 74478

African (AFR) AF: 0.00390 AC: 162 AN: 41562

American (AMR) AF: 0.000196 AC: 3 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000404 Hom.: 1

Bravo AF: 0.00113

ESP6500AA AF: 0.00340 AC: 15

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000329 AC: 40

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	PTPRS-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.74	D
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.0086	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.8
PrimateAI	Pathogenic	0.86	D
REVEL	Benign	0.23
Sift4G	Uncertain	0.033	D
Polyphen		1.0	D
Vest4		0.53
MVP		0.26
ClinPred		0.16	T
GERP RS		2.6
Varity_R		0.45
gMVP		0.67
Mutation Taster		=35/65	disease causing

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: rs148478353; hg19: chr19-5208335;