Variant 6-63578977-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003463.5(PTP4A1):c.278G>A(p.Arg93His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000933 in 1,607,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PTP4A1
NM_003463.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.91

Variant links:

Genes affected

PTP4A1 (HGNC:9634): (protein tyrosine phosphatase 4A1) This gene encodes a member of a small class of prenylated protein tyrosine phosphatases (PTPs), which contain a PTP domain and a characteristic C-terminal prenylation motif. The encoded protein is a cell signaling molecule that plays regulatory roles in a variety of cellular processes, including cell proliferation and migration. The protein may also be involved in cancer development and metastasis. This tyrosine phosphatase is a nuclear protein, but may associate with plasma membrane by means of its prenylation motif. Pseudogenes related to this gene are located on chromosomes 1, 2, 5, 7, 11 and X. [provided by RefSeq, Jun 2013]

PTP4A1 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

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=0.20839489).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTP4A1	NM_003463.5 linkuse as main transcript	c.278G>A	p.Arg93His	missense_variant	4/6	ENST00000626021.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTP4A1	ENST00000626021.3 linkuse as main transcript	c.278G>A	p.Arg93His	missense_variant	4/6	1	NM_003463.5	P1
	ENST00000370651.8 linkuse as main transcript	c.*627G>A		3_prime_UTR_variant	4/6	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000242

AC:

AN:

248146

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134316

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000332

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000618

AC:

AN:

1455498

Hom.:

Cov.:

AF XY:

0.00000691

AC XY:

AN XY:

724066

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.0000763

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2023

The c.278G>A (p.R93H) alteration is located in exon 4 (coding exon 3) of the PTP4A1 gene. This alteration results from a G to A substitution at nucleotide position 278, causing the arginine (R) at amino acid position 93 to be replaced by a histidine (H). 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

0.15

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

T;T;.

Eigen

Benign

0.089

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

.;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.5

L;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.77

Sift4G

Benign

0.70

.;T;T

Polyphen

0.0030

B;B;.

Vest4

0.64, 0.60

MutPred

0.27

Loss of ubiquitination at K91 (P = 0.0418);Loss of ubiquitination at K91 (P = 0.0418);Loss of ubiquitination at K91 (P = 0.0418);

MVP

0.88

ClinPred

0.37

GERP RS

5.8

Varity_R

0.39

gMVP

0.80

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over