7-77615014-C-G

Position:

• chr7-77615014-C-G

Variant summary

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

The NM_002835.4(PTPN12):​c.940-3466C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,022 control chromosomes in the GnomAD database, including 3,060 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 0.18 (3060 hom., cov: 32)
• Consequence: PTPN12 NM_002835.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN12	NM_002835.4	c.940-3466C>G		intron_variant		ENST00000248594.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN12	ENST00000248594.11	c.940-3466C>G		intron_variant		1	NM_002835.4	P1
PTPN12	ENST00000415482.6	c.583-3466C>G		intron_variant		5
PTPN12	ENST00000435495.6	c.550-3466C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27992 AN: 151904 Hom.: 3054 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.0354

Gnomad SAS AF: 0.0610

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.184 AC: 28032 AN: 152022 Hom.: 3060 Cov.: 32 AF XY: 0.181 AC XY: 13448 AN XY: 74334

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.0355

Gnomad4 SAS AF: 0.0611

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.165

Alfa AF: 0.164 Hom.: 279

Bravo AF: 0.186

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
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: rs17155601; hg19: chr7-77244331;