rs4886707

Variant names:

• chr15-75463126-C-T
• rs4886707
• NM_002833.4:c.*5643G>A

Variant summary

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

The NM_002833.4(PTPN9):​c.*5643G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,094 control chromosomes in the GnomAD database, including 9,173 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 0.33 (9169 hom., cov: 31)
  • Exomes 𝑓: 0.25 (4 hom.)
• Consequence: PTPN9 NM_002833.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770

Genes affected

PTPN9 (HGNC:9661): (protein tyrosine phosphatase non-receptor type 9) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains an N-terminal domain that shares a significant similarity with yeast SEC14, which is a protein that has phosphatidylinositol transfer activity and is required for protein secretion through the Golgi complex in yeast. This PTP was found to be activated by polyphosphoinositide, and is thought to be involved in signaling events regulating phagocytosis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN9	NM_002833.4	c.*5643G>A		downstream_gene_variant		ENST00000618819.5	NP_002824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN9	ENST00000618819.5	c.*5643G>A		downstream_gene_variant		1	NM_002833.4	ENSP00000482732.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50114 AN: 151846 Hom.: 9148 Cov.: 31

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.353

GnomAD4 exome AF: 0.246 AC: 32 AN: 130 Hom.: 4 AF XY: 0.271 AC XY: 26 AN XY: 96

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.330 AC: 50179 AN: 151964 Hom.: 9169 Cov.: 31 AF XY: 0.330 AC XY: 24540 AN XY: 74290

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.357

Alfa AF: 0.280 Hom.: 13676

Bravo AF: 0.338

Asia WGS AF: 0.379 AC: 1314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4886707; hg19: chr15-75755467;