NM_002835.4:c.1026-81T>C

Variant names:

• chr7-77626624-T-C
• rs17467232
• NM_002835.4:c.1026-81T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002835.4(PTPN12):​c.1026-81T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,413,330 control chromosomes in the GnomAD database, including 54,499 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 0.24 (4635 hom., cov: 32)
  • Exomes 𝑓: 0.28 (49864 hom.)
• Consequence: PTPN12 NM_002835.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN12	NM_002835.4	MANE Select	c.1026-81T>C		intron	N/A	NP_002826.3
	PTPN12	NM_001131008.2		c.669-81T>C		intron	N/A	NP_001124480.1	Q05209-3
	PTPN12	NM_001131009.2		c.636-81T>C		intron	N/A	NP_001124481.1	Q05209-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN12	ENST00000248594.11	TSL:1 MANE Select	c.1026-81T>C		intron	N/A	ENSP00000248594.6	Q05209-1
	PTPN12	ENST00000962769.1		c.1023-81T>C		intron	N/A	ENSP00000632828.1
	PTPN12	ENST00000962770.1		c.855-81T>C		intron	N/A	ENSP00000632829.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36603 AN: 151996 Hom.: 4631 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.278 AC: 351061 AN: 1261216 Hom.: 49864 AF XY: 0.278 AC XY: 172486 AN XY: 620698

African (AFR) AF: 0.177 AC: 4952 AN: 28018

American (AMR) AF: 0.249 AC: 6807 AN: 27324

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 4987 AN: 19116

East Asian (EAS) AF: 0.171 AC: 6501 AN: 37920

South Asian (SAS) AF: 0.263 AC: 16938 AN: 64448

European-Finnish (FIN) AF: 0.260 AC: 11905 AN: 45858

Middle Eastern (MID) AF: 0.229 AC: 1173 AN: 5114

European-Non Finnish (NFE) AF: 0.290 AC: 283950 AN: 980580

Other (OTH) AF: 0.262 AC: 13848 AN: 52838

GnomAD4 genome AF: 0.241 AC: 36631 AN: 152114 Hom.: 4635 Cov.: 32 AF XY: 0.237 AC XY: 17602 AN XY: 74370

African (AFR) AF: 0.181 AC: 7512 AN: 41504

American (AMR) AF: 0.242 AC: 3706 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 952 AN: 3470

East Asian (EAS) AF: 0.165 AC: 851 AN: 5170

South Asian (SAS) AF: 0.272 AC: 1312 AN: 4824

European-Finnish (FIN) AF: 0.242 AC: 2558 AN: 10572

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18976 AN: 67980

Other (OTH) AF: 0.247 AC: 519 AN: 2104

Alfa AF: 0.267 Hom.: 21200

Bravo AF: 0.236

Asia WGS AF: 0.239 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.44
PhyloP100		0.068
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: rs17467232; hg19: chr7-77255941;