Variant 12-120214923-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001385981.1(PXN):c.2650C>T(p.Arg884Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000793 in 1,613,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

PXN
NM_001385981.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17

Variant links:

Genes affected

PXN (HGNC:9718): (paxillin) This gene encodes a cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Alternatively spliced transcript variants encoding different isoforms have been described for this gene. These isoforms exhibit different expression pattern, and have different biochemical, as well as physiological properties (PMID:9054445). [provided by RefSeq, Aug 2011]

PXN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.808

BS2

High AC in GnomAdExome at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXN	NM_001385981.1 linkuse as main transcript	c.2650C>T	p.Arg884Trp	missense_variant	12/15	ENST00000637617.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXN	ENST00000637617.2 linkuse as main transcript	c.2650C>T	p.Arg884Trp	missense_variant	12/15	5	NM_001385981.1	A2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000442

AC:

AN:

248960

Hom.:

AF XY:

0.0000592

AC XY:

AN XY:

135168

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000848

AC:

124

AN:

1461688

Hom.:

Cov.:

AF XY:

0.0000894

AC XY:

AN XY:

727122

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:

0.000243

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000917

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

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

Mar 01, 2023

The c.1180C>T (p.R394W) alteration is located in exon 9 (coding exon 9) of the PXN gene. This alteration results from a C to T substitution at nucleotide position 1180, causing the arginine (R) at amino acid position 394 to be replaced by a tryptophan (W). 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

Pathogenic

0.88

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.25

Cadd

Pathogenic

Dann

Pathogenic

1.0

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.87

LIST_S2

Pathogenic

0.98

D;D;D;D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.81

D;D;D;D;D;D

MetaSVM

Uncertain

0.58

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-6.5

D;D;D;D;D;.

REVEL

Pathogenic

0.75

Sift

Uncertain

0.0020

D;D;D;D;D;.

Sift4G

Uncertain

0.0050

D;D;D;D;D;.

Polyphen

1.0

D;.;D;D;.;.

Vest4

0.75

MutPred

0.50

.;.;Gain of catalytic residue at I391 (P = 0.0014);.;.;.;

MVP

0.96

MPC

1.6

ClinPred

0.76

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.56

gMVP

0.61

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