rs6955503

Positions:

• chr7-77597924-C-T

Variant summary

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

The NM_002835.4(PTPN12):​c.552+23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,607,278 control chromosomes in the GnomAD database, including 63,934 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 0.26 (5382 hom., cov: 33)
  • Exomes 𝑓: 0.28 (58552 hom.)
• Consequence: PTPN12 NM_002835.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220

Genes affected

PTPN12 (HGNC:9645): (protein tyrosine phosphatase non-receptor type 12) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains a C-terminal PEST motif, which serves as a protein-protein interaction domain, and may regulate protein intracellular half-life. This PTP was found to bind and dephosphorylate the product of the oncogene c-ABL and thus may play a role in oncogenesis. This PTP was also shown to interact with, and dephosphorylate, various products related to cytoskeletal structure and cell adhesion, such as p130 (Cas), CAKbeta/PTK2B, PSTPIP1, and paxillin. This suggests it has a regulatory role in controlling cell shape and mobility. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN12	NM_002835.4	c.552+23C>T		intron_variant		ENST00000248594.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN12	ENST00000248594.11	c.552+23C>T		intron_variant		1	NM_002835.4	P1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 40016 AN: 152014 Hom.: 5372 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.264

GnomAD3 exomes AF: 0.265 AC: 65281 AN: 246088 Hom.: 8711 AF XY: 0.266 AC XY: 35350 AN XY: 133048

Gnomad AFR exome AF: 0.255

Gnomad AMR exome AF: 0.262

Gnomad ASJ exome AF: 0.259

Gnomad EAS exome AF: 0.158

Gnomad SAS exome AF: 0.276

Gnomad FIN exome AF: 0.261

Gnomad NFE exome AF: 0.284

Gnomad OTH exome AF: 0.267

GnomAD4 exome AF: 0.282 AC: 410486 AN: 1455148 Hom.: 58552 Cov.: 31 AF XY: 0.281 AC XY: 203512 AN XY: 723610

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.263

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.291

Gnomad4 OTH exome AF: 0.270

GnomAD4 genome AF: 0.263 AC: 40059 AN: 152130 Hom.: 5382 Cov.: 33 AF XY: 0.259 AC XY: 19254 AN XY: 74372

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.264

Alfa AF: 0.273 Hom.: 2906

Bravo AF: 0.262

Asia WGS AF: 0.243 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.78
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6955503; hg19: chr7-77227241; COSMIC: COSV50354488;