12-120212167-C-T

Variant names:

• chr12-120212167-C-T
• rs3742039
• NM_001385981.1:c.*147G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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:44123): (PXN antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXN	NM_001385981.1	MANE Select	c.*147G>A		3_prime_UTR	Exon 15 of 15	NP_001372910.1
	PXN	NM_001385982.1		c.*147G>A		3_prime_UTR	Exon 14 of 14	NP_001372911.1
	PXN	NM_001385983.1		c.*147G>A		3_prime_UTR	Exon 14 of 14	NP_001372912.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXN	ENST00000637617.2	TSL:5 MANE Select	c.*147G>A		3_prime_UTR	Exon 15 of 15	ENSP00000489840.1
	PXN	ENST00000228307.11	TSL:1	c.*147G>A		3_prime_UTR	Exon 12 of 12	ENSP00000228307.7
	PXN	ENST00000424649.6	TSL:1	c.*147G>A		3_prime_UTR	Exon 11 of 11	ENSP00000391283.2

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

African (AFR) AF: 0.146 AC: 3715 AN: 25360

American (AMR) AF: 0.429 AC: 13986 AN: 32632

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 9993 AN: 19814

East Asian (EAS) AF: 0.434 AC: 16027 AN: 36932

South Asian (SAS) AF: 0.636 AC: 43884 AN: 68976

European-Finnish (FIN) AF: 0.515 AC: 17768 AN: 34524

Middle Eastern (MID) AF: 0.531 AC: 1953 AN: 3676

European-Non Finnish (NFE) AF: 0.513 AC: 407852 AN: 794510

Other (OTH) AF: 0.489 AC: 23017 AN: 47048

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

African (AFR) AF: 0.164 AC: 6801 AN: 41460

American (AMR) AF: 0.449 AC: 6858 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1764 AN: 3464

East Asian (EAS) AF: 0.418 AC: 2143 AN: 5126

South Asian (SAS) AF: 0.635 AC: 3053 AN: 4810

European-Finnish (FIN) AF: 0.490 AC: 5186 AN: 10576

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34958 AN: 67920

Other (OTH) AF: 0.462 AC: 975 AN: 2112

Alfa AF: 0.480 Hom.: 68192

Bravo AF: 0.391

Asia WGS AF: 0.539 AC: 1873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.49
DANN	Benign	0.71
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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