Genetic Variant PTP4A1:c.-445-16494G>A (chr6-63559942-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001385254.1(PTP4A1):c.-445-16494G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,838 control chromosomes in the GnomAD database, including 5,748 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5748 hom., cov: 31)

Consequence

PTP4A1
NM_001385254.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.277

Publications

2 publications found

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:

LGSN (HGNC:21016): (lengsin, lens protein with glutamine synthetase domain) This gene encodes a protein with similarity to the GS I members of the glutamine synthetase superfamily. The encoded protein is referred to as a pseudo-glutamine synthetase because it has no glutamine synthesis activity and may function as a chaperone protein. This protein is localized to the lens and may be associated with cataract disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

LGSN links:

ENSG00000289911 (HGNC:):

ENSG00000289911 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385254.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
PTP4A1	NM_001385254.1	c.-445-16494G>A	intron	N/A	NP_001372183.1	Q93096
PTP4A1	NM_001385255.1	c.-446+9449G>A	intron	N/A	NP_001372184.1	Q93096
PTP4A1	NM_001385256.1	c.-445-16494G>A	intron	N/A	NP_001372185.1	Q93096

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PTP4A1	ENST00000648894.1		c.-445-16494G>A	intron	N/A	ENSP00000497588.1	Q93096
PTP4A1	ENST00000639568.2	TSL:5	c.-446+9449G>A	intron	N/A	ENSP00000497431.1	A0A3B3ISR8
PTP4A1	ENST00000470661.1	TSL:2	n.333-16494G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38446

AN:

151720

Hom.:

5741

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0852

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.275

Gnomad EAS

AF:

0.250

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.276

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.253

AC:

38452

AN:

151838

Hom.:

5748

Cov.:

AF XY:

0.253

AC XY:

18768

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.0850

AC:

3519

AN:

41424

American (AMR)

AF:

0.337

AC:

5131

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

955

AN:

3472

East Asian (EAS)

AF:

0.249

AC:

1280

AN:

5142

South Asian (SAS)

AF:

0.305

AC:

1467

AN:

4804

European-Finnish (FIN)

AF:

0.247

AC:

2597

AN:

10506

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.331

AC:

22458

AN:

67934

Other (OTH)

AF:

0.273

AC:

577

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1383

2765

4148

5530

6913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.290

Hom.:

4430

Bravo

AF:

0.253

Asia WGS

AF:

0.249

AC:

864

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.6

(source)

DANN

Benign

0.60

PhyloP100

-0.28

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over