rs1178015

Positions:

• chr20-3015777-T-A
• chr20-3015777-T-C

Variant summary

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

The NM_001385305.1(PTPRA):​c.907-72T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 1,315,550 control chromosomes in the GnomAD database, including 172,990 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 0.53 (21645 hom., cov: 32)
  • Exomes 𝑓: 0.50 (151345 hom.)
• Consequence: PTPRA NM_001385305.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRA	NM_001385305.1	c.907-72T>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.907-72T>A		intron_variant		5	NM_001385305.1	ENSP00000382787	P4
PTPRA	ENST00000216877.10	c.880-72T>A		intron_variant		1		ENSP00000216877	A1
PTPRA	ENST00000356147.3	c.880-72T>A		intron_variant		1		ENSP00000348468	A1
PTPRA	ENST00000318266.9	c.880-72T>A		intron_variant		5		ENSP00000314568	A1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80459 AN: 151896 Hom.: 21638 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.527

GnomAD4 exome AF: 0.504 AC: 586786 AN: 1163536 Hom.: 151345 AF XY: 0.507 AC XY: 300084 AN XY: 591358

Gnomad4 AFR exome AF: 0.543

Gnomad4 AMR exome AF: 0.533

Gnomad4 ASJ exome AF: 0.415

Gnomad4 EAS exome AF: 0.851

Gnomad4 SAS exome AF: 0.599

Gnomad4 FIN exome AF: 0.528

Gnomad4 NFE exome AF: 0.480

Gnomad4 OTH exome AF: 0.502

GnomAD4 genome AF: 0.530 AC: 80503 AN: 152014 Hom.: 21645 Cov.: 32 AF XY: 0.536 AC XY: 39834 AN XY: 74314

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.528

Alfa AF: 0.505 Hom.: 2365

Bravo AF: 0.531

Asia WGS AF: 0.646 AC: 2247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs1178015; hg19: chr20-2996423;