chr20-2909074-C-G

Variant names:

• chr20-2909074-C-G
• rs1016753
• NM_001385305.1:c.-128-14133C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001385305.1(PTPRA):​c.-128-14133C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 152,118 control chromosomes in the GnomAD database, including 318 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 0.043 (318 hom., cov: 32)
• Consequence: PTPRA NM_001385305.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRA	NM_001385305.1	c.-128-14133C>G		intron_variant	Intron 1 of 23	ENST00000399903.7	NP_001372234.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRA	ENST00000399903.7	c.-128-14133C>G		intron_variant	Intron 1 of 23	5	NM_001385305.1	ENSP00000382787.2

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 6440 AN: 152000 Hom.: 307 Cov.: 32

Gnomad AFR AF: 0.0875

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.0891

Gnomad SAS AF: 0.0421

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00362

Gnomad OTH AF: 0.0431

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0426 AC: 6480 AN: 152118 Hom.: 318 Cov.: 32 AF XY: 0.0443 AC XY: 3298 AN XY: 74368

African (AFR) AF: 0.0879 AC: 3645 AN: 41488

American (AMR) AF: 0.108 AC: 1646 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.0887 AC: 459 AN: 5176

South Asian (SAS) AF: 0.0415 AC: 200 AN: 4818

European-Finnish (FIN) AF: 0.0161 AC: 170 AN: 10582

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00362 AC: 246 AN: 67998

Other (OTH) AF: 0.0432 AC: 91 AN: 2108

Alfa AF: 0.0236 Hom.: 23

Bravo AF: 0.0523

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	7.3
DANN	Benign	0.95
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1016753; hg19: chr20-2889720;