Genetic Variant NM_001385981.1:c.3100G>A (chr12-120212460-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_001385981.1(PXN):c.3100G>A(p.Gly1034Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,864 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PXN
NM_001385981.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.84

Publications

2 publications found

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:

PXN-AS1 (HGNC:44123): (PXN antisense RNA 1)

PXN-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.816

BS2

High AC in GnomAdExome4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385981.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PXN	NM_001385981.1	MANE Select	c.3100G>A	p.Gly1034Ser	missense	Exon 15 of 15	NP_001372910.1	A0A1B0GTU4
PXN	NM_001385982.1		c.2824G>A	p.Gly942Ser	missense	Exon 14 of 14	NP_001372911.1
PXN	NM_001385983.1		c.2818G>A	p.Gly940Ser	missense	Exon 14 of 14	NP_001372912.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PXN	ENST00000637617.2	TSL:5 MANE Select	c.3100G>A	p.Gly1034Ser	missense	Exon 15 of 15	ENSP00000489840.1	A0A1B0GTU4
PXN	ENST00000228307.11	TSL:1	c.1630G>A	p.Gly544Ser	missense	Exon 12 of 12	ENSP00000228307.7	P49023-1
PXN	ENST00000424649.6	TSL:1	c.1528G>A	p.Gly510Ser	missense	Exon 11 of 11	ENSP00000391283.2	P49023-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000805

AC:

AN:

248370

AF XY:

0.00000741

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461682

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111868

Other (OTH)

AF:

0.0000166

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000826

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.24

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.89

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.82

MetaSVM

Uncertain

0.71

MutationAssessor

Uncertain

2.9

PhyloP100

7.8

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-5.5

REVEL

Pathogenic

0.79

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.65

MutPred

0.49

Gain of catalytic residue at R545 (P = 0)

MVP

0.98

MPC

1.6

ClinPred

0.99

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.77

gMVP

0.70

Mutation Taster

=43/57

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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