20-3026547-T-A

Variant names:

• chr20-3026547-T-A
• rs6138982
• NM_001385305.1:c.1615-140T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PTPRA	NM_001385305.1	c.1615-140T>A		intron_variant	Intron 17 of 23	ENST00000399903.7	NP_001372234.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRA	ENST00000399903.7	c.1615-140T>A		intron_variant	Intron 17 of 23	5	NM_001385305.1	ENSP00000382787.2
PTPRA	ENST00000216877.10	c.1588-140T>A		intron_variant	Intron 16 of 22	1		ENSP00000216877.6
PTPRA	ENST00000356147.3	c.1588-140T>A		intron_variant	Intron 16 of 22	1		ENSP00000348468.3
PTPRA	ENST00000318266.9	c.1588-140T>A		intron_variant	Intron 17 of 23	5		ENSP00000314568.5

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

African (AFR) AF: 0.109 AC: 1445 AN: 13232

American (AMR) AF: 0.215 AC: 4744 AN: 22056

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 2620 AN: 14416

East Asian (EAS) AF: 0.432 AC: 13355 AN: 30886

South Asian (SAS) AF: 0.254 AC: 11765 AN: 46326

European-Finnish (FIN) AF: 0.270 AC: 11067 AN: 40918

Middle Eastern (MID) AF: 0.259 AC: 933 AN: 3598

European-Non Finnish (NFE) AF: 0.236 AC: 67411 AN: 285964

Other (OTH) AF: 0.237 AC: 6409 AN: 27018

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

African (AFR) AF: 0.105 AC: 4366 AN: 41468

American (AMR) AF: 0.237 AC: 3612 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 623 AN: 3460

East Asian (EAS) AF: 0.393 AC: 2028 AN: 5166

South Asian (SAS) AF: 0.248 AC: 1191 AN: 4806

European-Finnish (FIN) AF: 0.267 AC: 2822 AN: 10572

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.233 AC: 15812 AN: 67964

Other (OTH) AF: 0.253 AC: 535 AN: 2112

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
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6138982; hg19: chr20-3007193;