15-75468800-C-T

Position:

• chr15-75468800-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002833.4(PTPN9):​c.1751G>A​(p.Gly584Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPN9 NM_002833.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07993841).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN9	NM_002833.4	c.1751G>A	p.Gly584Asp	missense_variant	13/13	ENST00000618819.5	NP_002824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN9	ENST00000618819.5	c.1751G>A	p.Gly584Asp	missense_variant	13/13	1	NM_002833.4	ENSP00000482732	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 23, 2023

The c.1751G>A (p.G584D) alteration is located in exon 13 (coding exon 13) of the PTPN9 gene. This alteration results from a G to A substitution at nucleotide position 1751, causing the glycine (G) at amino acid position 584 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.060	T;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.031
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.080	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.94	L;.
MutationTaster	Benign	0.62	N
PrimateAI	Benign	0.30	T
REVEL	Benign	0.029
Sift4G	Benign	0.92	T;T
Polyphen		0.030	B;.
Vest4		0.13
MutPred		0.39		Gain of solvent accessibility (P = 0.0149);.;
MVP		0.17
MPC		0.62
ClinPred		0.18	T
GERP RS		4.3
Varity_R		0.047
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr15-75761141;