rs11611541

chr12-120262686-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.13+2931G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,186 control chromosomes in the GnomAD database, including 1,650 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 0.14 (1650 hom., cov: 32)
• Consequence: PXN NM_001385981.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXN	NM_001385981.1	c.13+2931G>A		intron_variant		ENST00000637617.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXN	ENST00000637617.2	c.13+2931G>A		intron_variant		5	NM_001385981.1	A2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21286 AN: 152068 Hom.: 1652 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0718

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.134

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.140 AC: 21289 AN: 152186 Hom.: 1650 Cov.: 32 AF XY: 0.141 AC XY: 10490 AN XY: 74390

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0714

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.132

Alfa AF: 0.150 Hom.: 1770

Bravo AF: 0.133

Asia WGS AF: 0.0370 AC: 130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.4
Dann	Benign	0.74

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: rs11611541; hg19: chr12-120700489;