Variant 6-63578936-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003463.5(PTP4A1):c.237G>C(p.Gln79His) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,104 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PTP4A1
NM_003463.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.28

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36984634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTP4A1	NM_003463.5 linkuse as main transcript	c.237G>C	p.Gln79His	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.237G>C	p.Gln79His	missense_variant	4/6	1	NM_003463.5	P1
	ENST00000370651.8 linkuse as main transcript	c.*586G>C		3_prime_UTR_variant	4/6	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1447104

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719792

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

9.03e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 15, 2022

The c.237G>C (p.Q79H) alteration is located in exon 4 (coding exon 3) of the PTP4A1 gene. This alteration results from a G to C substitution at nucleotide position 237, causing the glutamine (Q) at amino acid position 79 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

0.26

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

T;T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

0.022

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.82

.;T;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.37

T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.4

L;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.77

Sift4G

Benign

0.092

.;T;T

Polyphen

0.0080

B;B;.

Vest4

0.60, 0.59

MutPred

0.36

Gain of catalytic residue at D82 (P = 0.0645);Gain of catalytic residue at D82 (P = 0.0645);Gain of catalytic residue at D82 (P = 0.0645);

MVP

0.51

ClinPred

0.62

GERP RS

4.0

Varity_R

0.47

gMVP

0.72

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