chr19-5210784-C-T

Variant names:

• chr19-5210784-C-T
• rs140704487
• NM_002850.4:c.5256G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_002850.4(PTPRS):​c.5256G>A​(p.Ala1752Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000295 in 1,613,986 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: PTPRS NM_002850.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.62
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 19-5210784-C-T is Benign according to our data. Variant chr19-5210784-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3048605.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.62 with no splicing effect.
• BS2: High AC in GnomAd4 at 252 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.5256G>A	p.Ala1752Ala	synonymous	Exon 34 of 38	NP_002841.3
	PTPRS	NM_001394011.1		c.5190G>A	p.Ala1730Ala	synonymous	Exon 30 of 34	NP_001380940.1
	PTPRS	NM_001394012.1		c.5169G>A	p.Ala1723Ala	synonymous	Exon 30 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.5256G>A	p.Ala1752Ala	synonymous	Exon 34 of 38	ENSP00000262963.8	Q13332-1
	PTPRS	ENST00000587303.5	TSL:1	c.5256G>A	p.Ala1752Ala	synonymous	Exon 33 of 37	ENSP00000467537.1	Q13332-1
	PTPRS	ENST00000588012.5	TSL:1	c.5142G>A	p.Ala1714Ala	synonymous	Exon 28 of 32	ENSP00000465443.1	Q13332-6

Frequencies

GnomAD3 genomes AF: 0.00165 AC: 251 AN: 152232 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00567

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000431 AC: 108 AN: 250854 AF XY: 0.000236

Gnomad AFR exome AF: 0.00567

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000153 AC: 224 AN: 1461636 Hom.: 0 Cov.: 33 AF XY: 0.000132 AC XY: 96 AN XY: 727144

African (AFR) AF: 0.00514 AC: 172 AN: 33480

American (AMR) AF: 0.000291 AC: 13 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111992

Other (OTH) AF: 0.000248 AC: 15 AN: 60390

GnomAD4 genome AF: 0.00165 AC: 252 AN: 152350 Hom.: 0 Cov.: 33 AF XY: 0.00154 AC XY: 115 AN XY: 74504

African (AFR) AF: 0.00568 AC: 236 AN: 41582

American (AMR) AF: 0.000719 AC: 11 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

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

Alfa AF: 0.000733 Hom.: 1

Bravo AF: 0.00184

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PTPRS-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	1.8
DANN	Benign	0.70
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs140704487; hg19: chr19-5210795; COSMIC: COSV53611611; COSMIC: COSV53611611;