7-77544804-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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.

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>A		intron	N/A	NP_002826.3
	PTPN12	NM_001131008.2		c.-259+6698G>A		intron	N/A	NP_001124480.1
	PTPN12	NM_001131009.2		c.-196+6698G>A		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>A		intron	N/A	ENSP00000248594.6
	PTPN12	ENST00000415482.6	TSL:5	c.-259+6698G>A		intron	N/A	ENSP00000392429.2
	PTPN12	ENST00000435495.6	TSL:2	c.-196+6698G>A		intron	N/A	ENSP00000397991.2

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

African (AFR) AF: 0.543 AC: 22526 AN: 41452

American (AMR) AF: 0.459 AC: 7012 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1279 AN: 3470

East Asian (EAS) AF: 0.738 AC: 3821 AN: 5180

South Asian (SAS) AF: 0.418 AC: 2015 AN: 4826

European-Finnish (FIN) AF: 0.248 AC: 2619 AN: 10580

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18060 AN: 67990

Other (OTH) AF: 0.387 AC: 817 AN: 2112

Alfa AF: 0.302 Hom.: 5022

Bravo AF: 0.408

Asia WGS AF: 0.568 AC: 1976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.78
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism (auto)

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;