rs41276864

Variant names:

• chr19-5211601-A-G
• rs41276864
• NM_002850.4:c.5223T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-5211601-A-G
• chr19-5211601-A-C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002850.4(PTPRS):​c.5223T>C​(p.Ile1741Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,608,126 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0075 (9 hom., cov: 33)
  • Exomes 𝑓: 0.011 (133 hom.)
• Consequence: PTPRS NM_002850.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.272
• Publications: 3 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 19-5211601-A-G is Benign according to our data. Variant chr19-5211601-A-G is described in ClinVar as Benign. ClinVar VariationId is 782049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.272 with no splicing effect.
• BS2: High AC in GnomAd4 at 1140 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.5223T>C	p.Ile1741Ile	synonymous	Exon 33 of 38	NP_002841.3
	PTPRS	NM_001394011.1		c.5157T>C	p.Ile1719Ile	synonymous	Exon 29 of 34	NP_001380940.1
	PTPRS	NM_001394012.1		c.5136T>C	p.Ile1712Ile	synonymous	Exon 29 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.5223T>C	p.Ile1741Ile	synonymous	Exon 33 of 38	ENSP00000262963.8	Q13332-1
	PTPRS	ENST00000587303.5	TSL:1	c.5223T>C	p.Ile1741Ile	synonymous	Exon 32 of 37	ENSP00000467537.1	Q13332-1
	PTPRS	ENST00000588012.5	TSL:1	c.5109T>C	p.Ile1703Ile	synonymous	Exon 27 of 32	ENSP00000465443.1	Q13332-6

Frequencies

GnomAD3 genomes AF: 0.00750 AC: 1141 AN: 152200 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00817 AC: 2050 AN: 250954 AF XY: 0.00849

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.0210

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0125

Gnomad NFE exome AF: 0.0113

Gnomad OTH exome AF: 0.00801

GnomAD4 exome AF: 0.0111 AC: 16211 AN: 1455808 Hom.: 133 Cov.: 33 AF XY: 0.0108 AC XY: 7832 AN XY: 722804

African (AFR) AF: 0.00147 AC: 49 AN: 33352

American (AMR) AF: 0.00280 AC: 125 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 559 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39500

South Asian (SAS) AF: 0.00404 AC: 348 AN: 86170

European-Finnish (FIN) AF: 0.0134 AC: 714 AN: 53282

Middle Eastern (MID) AF: 0.00244 AC: 14 AN: 5736

European-Non Finnish (NFE) AF: 0.0125 AC: 13848 AN: 1107062

Other (OTH) AF: 0.00924 AC: 554 AN: 59986

GnomAD4 genome AF: 0.00748 AC: 1140 AN: 152318 Hom.: 9 Cov.: 33 AF XY: 0.00726 AC XY: 541 AN XY: 74480

African (AFR) AF: 0.00212 AC: 88 AN: 41576

American (AMR) AF: 0.00229 AC: 35 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00352 AC: 17 AN: 4824

European-Finnish (FIN) AF: 0.0121 AC: 129 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0113 AC: 768 AN: 68024

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.0107 Hom.: 3

Bravo AF: 0.00644

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0104

EpiControl AF: 0.0104

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	PTPRS-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.0
DANN	Benign	0.61
PhyloP100		-0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs41276864; hg19: chr19-5211612; COSMIC: COSV99508547; COSMIC: COSV99508547;