rs6138982

Positions:

• chr20-3026547-T-A
• chr20-3026547-T-C
• chr20-3026547-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385305.1(PTPRA):​c.1615-140T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 636,430 control chromosomes in the GnomAD database, including 19,366 homozygotes. 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: 𝑓 0.21 (3640 hom., cov: 31)
  • Exomes 𝑓: 0.25 (15726 hom.)
• Consequence: PTPRA NM_001385305.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295

Genes affected

PTPRA (HGNC:9664): (protein tyrosine phosphatase receptor type A) 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 domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. This PTP has been shown to dephosphorylate and activate Src family tyrosine kinases, and is implicated in the regulation of integrin signaling, cell adhesion and proliferation. Three alternatively spliced variants of this gene, which encode two distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRA	NM_001385305.1	c.1615-140T>A		intron_variant		ENST00000399903.7	NP_001372234.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRA	ENST00000399903.7	c.1615-140T>A		intron_variant		5	NM_001385305.1	ENSP00000382787	P4
PTPRA	ENST00000216877.10	c.1588-140T>A		intron_variant		1		ENSP00000216877	A1
PTPRA	ENST00000356147.3	c.1588-140T>A		intron_variant		1		ENSP00000348468	A1
PTPRA	ENST00000318266.9	c.1588-140T>A		intron_variant		5		ENSP00000314568	A1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31251 AN: 151898 Hom.: 3634 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.247 AC: 119749 AN: 484414 Hom.: 15726 AF XY: 0.247 AC XY: 63010 AN XY: 255010

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.432

Gnomad4 SAS exome AF: 0.254

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.206 AC: 31276 AN: 152016 Hom.: 3640 Cov.: 31 AF XY: 0.211 AC XY: 15704 AN XY: 74296

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.253

Alfa AF: 0.0962 Hom.: 118

Bravo AF: 0.202

Asia WGS AF: 0.277 AC: 964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.5
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs6138982; hg19: chr20-3007193;