rs1468682

Positions:

• chr7-77544804-G-A
• chr7-77544804-G-C

Variant summary

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

The NM_002835.4(PTPN12):​c.99+7159G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,084 control chromosomes in the GnomAD database, including 12,858 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 0.39 (12858 hom., cov: 33)
• Consequence: PTPN12 NM_002835.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.497

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=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN12	NM_002835.4	c.99+7159G>A		intron_variant		ENST00000248594.11	NP_002826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN12	ENST00000248594.11	c.99+7159G>A		intron_variant		1	NM_002835.4	ENSP00000248594.6

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58622 AN: 151966 Hom.: 12844 Cov.: 33

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.386 AC: 58677 AN: 152084 Hom.: 12858 Cov.: 33 AF XY: 0.390 AC XY: 29005 AN XY: 74354

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.387

Alfa AF: 0.269 Hom.: 2603

Bravo AF: 0.408

Asia WGS AF: 0.568 AC: 1976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.78

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: rs1468682; hg19: chr7-77174121;