rs143032580

Variant names:

• chr7-77600660-G-A
• rs143032580
• NM_002835.4:c.553-4G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002835.4(PTPN12):​c.553-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00902 in 1,576,236 control chromosomes in the GnomAD database, including 73 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0093 (65 hom.)
• Consequence: PTPN12 NM_002835.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001136
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.173
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 7-77600660-G-A is Benign according to our data. Variant chr7-77600660-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3024795.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 964 AD gene.

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.553-4G>A		splice_region intron	N/A	NP_002826.3
	PTPN12	NM_001131008.2		c.196-4G>A		splice_region intron	N/A	NP_001124480.1	Q05209-3
	PTPN12	NM_001131009.2		c.163-4G>A		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.553-4G>A		splice_region intron	N/A	ENSP00000248594.6	Q05209-1
	PTPN12	ENST00000962769.1		c.550-4G>A		splice_region intron	N/A	ENSP00000632828.1
	PTPN12	ENST00000962770.1		c.382-4G>A		splice_region intron	N/A	ENSP00000632829.1

Frequencies

GnomAD3 genomes AF: 0.00635 AC: 962 AN: 151614 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00196

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00310

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00480

Gnomad FIN AF: 0.0111

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00953

Gnomad OTH AF: 0.00528

GnomAD2 exomes AF: 0.00622 AC: 1357 AN: 218014 AF XY: 0.00655

Gnomad AFR exome AF: 0.00181

Gnomad AMR exome AF: 0.00166

Gnomad ASJ exome AF: 0.00799

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0104

Gnomad NFE exome AF: 0.00847

Gnomad OTH exome AF: 0.00553

GnomAD4 exome AF: 0.00930 AC: 13247 AN: 1424504 Hom.: 65 Cov.: 29 AF XY: 0.00914 AC XY: 6465 AN XY: 707374

African (AFR) AF: 0.00108 AC: 34 AN: 31438

American (AMR) AF: 0.00203 AC: 71 AN: 35032

Ashkenazi Jewish (ASJ) AF: 0.00857 AC: 209 AN: 24382

East Asian (EAS) AF: 0.0000510 AC: 2 AN: 39218

South Asian (SAS) AF: 0.00558 AC: 444 AN: 79532

European-Finnish (FIN) AF: 0.00901 AC: 475 AN: 52694

Middle Eastern (MID) AF: 0.00108 AC: 6 AN: 5576

European-Non Finnish (NFE) AF: 0.0105 AC: 11539 AN: 1097954

Other (OTH) AF: 0.00796 AC: 467 AN: 58678

GnomAD4 genome AF: 0.00635 AC: 964 AN: 151732 Hom.: 8 Cov.: 32 AF XY: 0.00637 AC XY: 472 AN XY: 74124

African (AFR) AF: 0.00196 AC: 81 AN: 41386

American (AMR) AF: 0.00310 AC: 47 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.00577 AC: 20 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00522 AC: 25 AN: 4792

European-Finnish (FIN) AF: 0.0111 AC: 117 AN: 10510

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00953 AC: 647 AN: 67916

Other (OTH) AF: 0.00522 AC: 11 AN: 2106

Alfa AF: 0.00806 Hom.: 5

Bravo AF: 0.00579

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	PTPN12-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.1
DANN	Benign	0.71
PhyloP100		0.17
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.0040
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: rs143032580; hg19: chr7-77229977;