NM_002835.4:c.99+7159G>C

Variant names:

• chr7-77544804-G-C
• rs1468682
• NM_002835.4:c.99+7159G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002835.4(PTPN12):​c.99+7159G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: PTPN12 NM_002835.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.497
• Publications: 5 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002835.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN12	NM_002835.4	MANE Select	c.99+7159G>C		intron	N/A	NP_002826.3
	PTPN12	NM_001131008.2		c.-259+6698G>C		intron	N/A	NP_001124480.1
	PTPN12	NM_001131009.2		c.-196+6698G>C		intron	N/A	NP_001124481.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN12	ENST00000248594.11	TSL:1 MANE Select	c.99+7159G>C		intron	N/A	ENSP00000248594.6
	PTPN12	ENST00000415482.6	TSL:5	c.-259+6698G>C		intron	N/A	ENSP00000392429.2
	PTPN12	ENST00000435495.6	TSL:2	c.-196+6698G>C		intron	N/A	ENSP00000397991.2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 5022

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		0.50

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: rs1468682; hg19: chr7-77174121;