rs17467232

Positions:

• chr7-77626624-T-C

Variant summary

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

The NM_002835.4(PTPN12):​c.1026-81T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,413,330 control chromosomes in the GnomAD database, including 54,499 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 0.24 (4635 hom., cov: 32)
  • Exomes 𝑓: 0.28 (49864 hom.)
• Consequence: PTPN12 NM_002835.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680

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]

PTPN12 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN12	NM_002835.4	c.1026-81T>C		intron_variant		ENST00000248594.11	NP_002826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN12	ENST00000248594.11	c.1026-81T>C		intron_variant		1	NM_002835.4	ENSP00000248594.6
PTPN12	ENST00000415482.6	c.669-81T>C		intron_variant		5		ENSP00000392429.2
PTPN12	ENST00000435495.6	c.636-81T>C		intron_variant		2		ENSP00000397991.2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36603 AN: 151996 Hom.: 4631 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.278 AC: 351061 AN: 1261216 Hom.: 49864 AF XY: 0.278 AC XY: 172486 AN XY: 620698

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.249

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.260

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.262

GnomAD4 genome AF: 0.241 AC: 36631 AN: 152114 Hom.: 4635 Cov.: 32 AF XY: 0.237 AC XY: 17602 AN XY: 74370

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.247

Alfa AF: 0.271 Hom.: 9664

Bravo AF: 0.236

Asia WGS AF: 0.239 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.44

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: rs17467232; hg19: chr7-77255941;