rs4729535

Positions:

• chr7-77560284-G-A

Variant summary

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

The NM_002835.4(PTPN12):​c.100-10794G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,964 control chromosomes in the GnomAD database, including 14,442 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 0.42 (14442 hom., cov: 32)
• Consequence: PTPN12 NM_002835.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN12	NM_002835.4	c.100-10794G>A		intron_variant		ENST00000248594.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN12	ENST00000248594.11	c.100-10794G>A		intron_variant		1	NM_002835.4	P1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63161 AN: 151846 Hom.: 14425 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.416 AC: 63218 AN: 151964 Hom.: 14442 Cov.: 32 AF XY: 0.421 AC XY: 31283 AN XY: 74284

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.420

Alfa AF: 0.342 Hom.: 5566

Bravo AF: 0.435

Asia WGS AF: 0.576 AC: 2001 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.7
DANN	Benign	0.37

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: rs4729535; hg19: chr7-77189601;