rs10485604

Positions:

• chr20-2955558-T-A

Variant summary

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

The NM_001385305.1(PTPRA):​c.-7+7534T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00549 in 889,674 control chromosomes in the GnomAD database, including 171 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 0.023 (125 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (46 hom.)
• Consequence: PTPRA NM_001385305.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.860

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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRA	NM_001385305.1	c.-7+7534T>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.-7+7534T>A		intron_variant		5	NM_001385305.1	ENSP00000382787	P4

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3448 AN: 152224 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00922

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.00194 AC: 1434 AN: 737332 Hom.: 46 AF XY: 0.00182 AC XY: 624 AN XY: 342490

Gnomad4 AFR exome AF: 0.0833

Gnomad4 AMR exome AF: 0.00703

Gnomad4 ASJ exome AF: 0.0148

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000138

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000120

Gnomad4 OTH exome AF: 0.00549

GnomAD4 genome AF: 0.0226 AC: 3450 AN: 152342 Hom.: 125 Cov.: 32 AF XY: 0.0214 AC XY: 1598 AN XY: 74508

Gnomad4 AFR AF: 0.0769

Gnomad4 AMR AF: 0.00914

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0135 Hom.: 6

Bravo AF: 0.0256

Asia WGS AF: 0.00635 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.86

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: rs10485604; hg19: chr20-2936204;