Variant chr12-120221685-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001385981.1(PXN):c.769A>G(p.Ile257Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000707 in 1,415,182 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: 0.0000071 ( 0 hom. )

Consequence

PXN
NM_001385981.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.40

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27814856).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXN	NM_001385981.1 linkuse as main transcript	c.769A>G	p.Ile257Val	missense_variant	6/15	ENST00000637617.2
LOC124903034	XR_007063486.1 linkuse as main transcript	n.1206T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXN	ENST00000637617.2 linkuse as main transcript	c.769A>G	p.Ile257Val	missense_variant	6/15	5	NM_001385981.1	A2
	ENST00000651205.1 linkuse as main transcript	n.1367T>C		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000566

AC:

AN:

176668

Hom.:

AF XY:

0.00

AC XY:

AN XY:

94604

show subpopulations

Gnomad AFR exome

AF:

0.000102

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000707

AC:

AN:

1415182

Hom.:

Cov.:

AF XY:

0.00000429

AC XY:

AN XY:

699836

show subpopulations

Gnomad4 AFR exome

AF:

0.0000309

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:

0.00000735

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 20, 2021

The c.769A>G (p.I257V) alteration is located in exon 6 (coding exon 6) of the PXN gene. This alteration results from a A to G substitution at nucleotide position 769, causing the isoleucine (I) at amino acid position 257 to be replaced by a valine (V). 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

0.18

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

.;.;T;.;T;T;.

Eigen

Benign

0.053

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.92

D;T;D;T;D;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.28

T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.3

M;.;M;M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.0

N;N;N;N;N;.;.

REVEL

Benign

0.081

Sift

Benign

0.51

T;T;T;T;T;.;.

Sift4G

Benign

0.63

T;T;T;T;T;.;.

Polyphen

0.012

B;.;B;B;.;.;.

Vest4

0.24

MutPred

0.24

Gain of catalytic residue at R256 (P = 0.0051);.;Gain of catalytic residue at R256 (P = 0.0051);Gain of catalytic residue at R256 (P = 0.0051);.;Gain of catalytic residue at R256 (P = 0.0051);.;

MVP

0.68

MPC

0.053

ClinPred

0.74

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.051

gMVP

0.21

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