19-5212471-G-C

Variant names:

• chr19-5212471-G-C
• rs2230611
• NM_002850.4:c.4635C>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PM2 BP4_Strong BP7 BS2

The NM_002850.4(PTPRS):​c.4635C>G​(p.Arg1545Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000347 in 1,441,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: PTPRS NM_002850.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.78
• Publications: 15 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 -7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-4.78 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.4635C>G	p.Arg1545Arg	synonymous_variant	Exon 31 of 38	ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.4635C>G	p.Arg1545Arg	synonymous_variant	Exon 31 of 38	5	NM_002850.4	ENSP00000262963.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000233 AC: 5 AN: 214790 AF XY: 0.0000172

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000162

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: 0.00000347 AC: 5 AN: 1441256 Hom.: 0 Cov.: 35 AF XY: 0.00000280 AC XY: 2 AN XY: 715142

African (AFR) AF: 0.00 AC: 0 AN: 32980

American (AMR) AF: 0.000120 AC: 5 AN: 41638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25772

East Asian (EAS) AF: 0.00 AC: 0 AN: 38634

South Asian (SAS) AF: 0.00 AC: 0 AN: 83572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101918

Other (OTH) AF: 0.00 AC: 0 AN: 59556

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.099
DANN	Benign	0.76
PhyloP100		-4.8

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: rs2230611; hg19: chr19-5212482;