12-120212167-C-T

Position:

• chr12-120212167-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385981.1(PXN):​c.*147G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 1,215,434 control chromosomes in the GnomAD database, including 154,173 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 0.41 (14795 hom., cov: 32)
  • Exomes 𝑓: 0.51 (139378 hom.)
• Consequence: PXN NM_001385981.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXN	NM_001385981.1	c.*147G>A		3_prime_UTR_variant	15/15	ENST00000637617.2	NP_001372910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXN	ENST00000637617	c.*147G>A		3_prime_UTR_variant	15/15	5	NM_001385981.1	ENSP00000489840.1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62467 AN: 151844 Hom.: 14783 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.456

GnomAD4 exome AF: 0.506 AC: 538195 AN: 1063472 Hom.: 139378 Cov.: 14 AF XY: 0.513 AC XY: 274830 AN XY: 536122

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.429

Gnomad4 ASJ exome AF: 0.504

Gnomad4 EAS exome AF: 0.434

Gnomad4 SAS exome AF: 0.636

Gnomad4 FIN exome AF: 0.515

Gnomad4 NFE exome AF: 0.513

Gnomad4 OTH exome AF: 0.489

GnomAD4 genome AF: 0.411 AC: 62497 AN: 151962 Hom.: 14795 Cov.: 32 AF XY: 0.413 AC XY: 30645 AN XY: 74276

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.462

Alfa AF: 0.497 Hom.: 30793

Bravo AF: 0.391

Asia WGS AF: 0.539 AC: 1873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.49
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs3742039; hg19: chr12-120649970; COSMIC: COSV57222870; COSMIC: COSV57222870;