Variant 12-120224174-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001385981.1(PXN):c.217A>G(p.Ser73Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 1,593,326 control chromosomes in the GnomAD database, including 508,349 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.84 ( 53937 hom., cov: 31)

Exomes 𝑓: 0.79 ( 454412 hom. )

Consequence

PXN
NM_001385981.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0780

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:

LOC124903034 (HGNC:):

LOC124903034 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.473439E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXN	NM_001385981.1 linkuse as main transcript	c.217A>G	p.Ser73Gly	missense_variant	2/15	ENST00000637617.2	NP_001372910.1
LOC124903034	XR_007063486.1 linkuse as main transcript	n.3695T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXN	ENST00000637617.2 linkuse as main transcript	c.217A>G	p.Ser73Gly	missense_variant	2/15	5	NM_001385981.1	ENSP00000489840	A2

Frequencies

GnomAD3 genomes

AF:

0.838

AC:

127340

AN:

151952

Hom.:

53874

Cov.:

show subpopulations

Gnomad AFR

AF:

0.947

Gnomad AMI

AF:

0.887

Gnomad AMR

AF:

0.817

Gnomad ASJ

AF:

0.847

Gnomad EAS

AF:

0.986

Gnomad SAS

AF:

0.908

Gnomad FIN

AF:

0.768

Gnomad MID

AF:

0.816

Gnomad NFE

AF:

0.770

Gnomad OTH

AF:

0.836

GnomAD3 exomes

AF:

0.831

AC:

179716

AN:

216210

Hom.:

75207

AF XY:

0.830

AC XY:

97388

AN XY:

117284

show subpopulations

Gnomad AFR exome

AF:

0.952

Gnomad AMR exome

AF:

0.861

Gnomad ASJ exome

AF:

0.845

Gnomad EAS exome

AF:

0.986

Gnomad SAS exome

AF:

0.898

Gnomad FIN exome

AF:

0.771

Gnomad NFE exome

AF:

0.773

Gnomad OTH exome

AF:

0.808

GnomAD4 exome

AF:

0.792

AC:

1141412

AN:

1441256

Hom.:

454412

Cov.:

AF XY:

0.794

AC XY:

568119

AN XY:

715082

show subpopulations

Gnomad4 AFR exome

AF:

0.955

Gnomad4 AMR exome

AF:

0.856

Gnomad4 ASJ exome

AF:

0.843

Gnomad4 EAS exome

AF:

0.987

Gnomad4 SAS exome

AF:

0.898

Gnomad4 FIN exome

AF:

0.771

Gnomad4 NFE exome

AF:

0.768

Gnomad4 OTH exome

AF:

0.813

GnomAD4 genome

AF:

0.838

AC:

127464

AN:

152070

Hom.:

53937

Cov.:

AF XY:

0.840

AC XY:

62380

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.947

Gnomad4 AMR

AF:

0.818

Gnomad4 ASJ

AF:

0.847

Gnomad4 EAS

AF:

0.986

Gnomad4 SAS

AF:

0.908

Gnomad4 FIN

AF:

0.768

Gnomad4 NFE

AF:

0.770

Gnomad4 OTH

AF:

0.837

Alfa

AF:

0.794

Hom.:

117546

Bravo

AF:

0.847

TwinsUK

AF:

0.777

AC:

2880

ALSPAC

AF:

0.750

AC:

2891

ESP6500AA

AF:

0.944

AC:

3593

ESP6500EA

AF:

0.777

AC:

6378

ExAC

AF:

0.817

AC:

97636

Asia WGS

AF:

0.938

AC:

3260

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.59

DANN

Benign

0.16

DEOGEN2

Benign

0.17

.;T;.;T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.088

T;T;T;T;T;T

MetaRNN

Benign

6.5e-7

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N;N;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.020

N;N;N;N;.;N

REVEL

Benign

0.030

Sift

Benign

0.88

T;T;T;T;.;T

Sift4G

Benign

0.52

T;T;T;T;.;.

Polyphen

0.0

.;B;B;.;.;.

Vest4

0.14

MPC

0.054

ClinPred

0.0039

GERP RS

0.22

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.13

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over