7-77571075-A-T

Variant names:

• chr7-77571075-A-T
• rs17155183
• NM_002835.4:c.100-3A>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BA1

The NM_002835.4(PTPN12):​c.100-3A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,526,904 control chromosomes in the GnomAD database, including 60,545 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.26 (5405 hom., cov: 33)
  • Exomes 𝑓: 0.28 (55140 hom.)
• Consequence: PTPN12 NM_002835.4 splice_region, intron
• Scores: Splicing: ADA: 0.002689
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.60
• Publications: 14 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 7-77571075-A-T is Benign according to our data. Variant chr7-77571075-A-T is described in ClinVar as Benign. ClinVar VariationId is 3059642.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 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.100-3A>T		splice_region intron	N/A	NP_002826.3
	PTPN12	NM_001131008.2		c.-258-3A>T		splice_region intron	N/A	NP_001124480.1	Q05209-3
	PTPN12	NM_001131009.2		c.-195-3A>T		splice_region 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.100-3A>T		splice_region intron	N/A	ENSP00000248594.6	Q05209-1
	PTPN12	ENST00000962769.1		c.100-3A>T		splice_region intron	N/A	ENSP00000632828.1
	PTPN12	ENST00000962770.1		c.100-3A>T		splice_region intron	N/A	ENSP00000632829.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40176 AN: 151946 Hom.: 5394 Cov.: 33

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.266

GnomAD2 exomes AF: 0.263 AC: 52056 AN: 197720 AF XY: 0.263

Gnomad AFR exome AF: 0.256

Gnomad AMR exome AF: 0.254

Gnomad ASJ exome AF: 0.248

Gnomad EAS exome AF: 0.156

Gnomad FIN exome AF: 0.261

Gnomad NFE exome AF: 0.282

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.281 AC: 386420 AN: 1374842 Hom.: 55140 Cov.: 23 AF XY: 0.280 AC XY: 191997 AN XY: 685490

African (AFR) AF: 0.253 AC: 7298 AN: 28884

American (AMR) AF: 0.252 AC: 7479 AN: 29622

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 6072 AN: 24016

East Asian (EAS) AF: 0.171 AC: 6288 AN: 36804

South Asian (SAS) AF: 0.262 AC: 19866 AN: 75784

European-Finnish (FIN) AF: 0.262 AC: 13783 AN: 52702

Middle Eastern (MID) AF: 0.237 AC: 1311 AN: 5526

European-Non Finnish (NFE) AF: 0.290 AC: 308964 AN: 1064604

Other (OTH) AF: 0.270 AC: 15359 AN: 56900

GnomAD4 genome AF: 0.265 AC: 40223 AN: 152062 Hom.: 5405 Cov.: 33 AF XY: 0.260 AC XY: 19325 AN XY: 74324

African (AFR) AF: 0.259 AC: 10753 AN: 41474

American (AMR) AF: 0.257 AC: 3923 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 933 AN: 3472

East Asian (EAS) AF: 0.164 AC: 848 AN: 5176

South Asian (SAS) AF: 0.273 AC: 1317 AN: 4820

European-Finnish (FIN) AF: 0.243 AC: 2565 AN: 10564

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.281 AC: 19080 AN: 67972

Other (OTH) AF: 0.265 AC: 560 AN: 2110

Alfa AF: 0.271 Hom.: 1776

Bravo AF: 0.264

Asia WGS AF: 0.242 AC: 841 AN: 3466

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PTPN12-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.86
PhyloP100		2.6
PromoterAI		0.0026	Neutral
Mutation Taster		=50/50	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0027
dbscSNV1_RF	Benign	0.012
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: rs17155183; hg19: chr7-77200392; COSMIC: COSV50354485;