15-75505874-G-C

Variant names:

• chr15-75505874-G-C
• NM_002833.4:c.769C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002833.4(PTPN9):​c.769C>G​(p.His257Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PTPN9 NM_002833.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.16

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN9	NM_002833.4	c.769C>G	p.His257Asp	missense_variant	Exon 7 of 13	ENST00000618819.5	NP_002824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN9	ENST00000618819.5	c.769C>G	p.His257Asp	missense_variant	Exon 7 of 13	1	NM_002833.4	ENSP00000482732.1
PTPN9	ENST00000564970.1	n.-58C>G		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727244

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	1.9	M;.
PrimateAI	Uncertain	0.56	T
REVEL	Uncertain	0.40
Sift4G	Benign	0.47	T;T
Polyphen		0.92	P;.
Vest4		0.55
MutPred		0.56		Loss of catalytic residue at H257 (P = 0.0297);.;
MVP		0.34
MPC		0.91
ClinPred		0.91	D
GERP RS		5.9
Varity_R		0.17
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-75798215; COSMIC: COSV60723759; COSMIC: COSV60723759;