rs149279759

Variant names:

• chr15-75505702-T-A
• rs149279759
• NM_002833.4:c.941A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002833.4(PTPN9):​c.941A>T​(p.Asn314Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,613,916 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0011 (1 hom.)
• Consequence: PTPN9 NM_002833.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018974334).
• BS2: High AC in GnomAd4 at 86 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002833.4. 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
	PTPN9	NM_002833.4	MANE Select	c.941A>T	p.Asn314Ile	missense	Exon 7 of 13	NP_002824.1	P43378

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN9	ENST00000618819.5	TSL:1 MANE Select	c.941A>T	p.Asn314Ile	missense	Exon 7 of 13	ENSP00000482732.1	P43378
	PTPN9	ENST00000944252.1		c.1058A>T	p.Asn353Ile	missense	Exon 8 of 14	ENSP00000614311.1
	PTPN9	ENST00000893935.1		c.941A>T	p.Asn314Ile	missense	Exon 7 of 14	ENSP00000563994.1

Frequencies

GnomAD3 genomes AF: 0.000566 AC: 86 AN: 152044 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000597 AC: 150 AN: 251160 AF XY: 0.000656

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00107

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.00106 AC: 1554 AN: 1461754 Hom.: 1 Cov.: 31 AF XY: 0.00101 AC XY: 733 AN XY: 727168

African (AFR) AF: 0.000119 AC: 4 AN: 33476

American (AMR) AF: 0.000648 AC: 29 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00132 AC: 1467 AN: 1111928

Other (OTH) AF: 0.000878 AC: 53 AN: 60394

GnomAD4 genome AF: 0.000565 AC: 86 AN: 152162 Hom.: 0 Cov.: 31 AF XY: 0.000430 AC XY: 32 AN XY: 74396

African (AFR) AF: 0.000241 AC: 10 AN: 41518

American (AMR) AF: 0.000458 AC: 7 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000927 AC: 63 AN: 67990

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.000759 Hom.: 0

Bravo AF: 0.000593

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.00175 AC: 15

ExAC AF: 0.000667 AC: 81

EpiCase AF: 0.00136

EpiControl AF: 0.00166

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.11	N
PhyloP100		2.3
PrimateAI	Uncertain	0.62	T
REVEL	Benign	0.025
Sift4G	Uncertain	0.050	T
Polyphen		0.10	B
Vest4		0.26
MVP		0.29
MPC		0.56
ClinPred		0.020	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.43
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs149279759; hg19: chr15-75798043; COSMIC: COSV100144622;