20-3024596-A-G

Position:

• chr20-3024596-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001385305.1(PTPRA):​c.1589A>G​(p.Asn530Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PTPRA NM_001385305.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.78

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0480538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRA	NM_001385305.1	c.1589A>G	p.Asn530Ser	missense_variant	17/24	ENST00000399903.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRA	ENST00000399903.7	c.1589A>G	p.Asn530Ser	missense_variant	17/24	5	NM_001385305.1	P4
PTPRA	ENST00000216877.10	c.1562A>G	p.Asn521Ser	missense_variant	16/23	1		A1
PTPRA	ENST00000356147.3	c.1562A>G	p.Asn521Ser	missense_variant	16/23	1		A1
PTPRA	ENST00000318266.9	c.1562A>G	p.Asn521Ser	missense_variant	17/24	5		A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461884 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2023

The c.1589A>G (p.N530S) alteration is located in exon 21 (coding exon 14) of the PTPRA gene. This alteration results from a A to G substitution at nucleotide position 1589, causing the asparagine (N) at amino acid position 530 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.17	T;.;T;.;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.070
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.88	.;.;D;.;D
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.048	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.2	N;.;N;.;.
MutationTaster	Benign	0.94	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.10	N;N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.77	T;T;T;T;T
Sift4G	Benign	0.73	T;T;T;T;T
Polyphen		0.0	B;.;B;.;.
Vest4		0.042
MVP		0.33
MPC		0.51
ClinPred		0.49	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.067
gMVP		0.066

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: rs778743622; hg19: chr20-3005242;