rs1634815

Positions:

• chr12-120249277-G-C
• chr12-120249277-G-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+16340C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,078 control chromosomes in the GnomAD database, including 7,833 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 0.27 (7833 hom., cov: 31)
• Consequence: PXN NM_001385981.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.17

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXN	NM_001385981.1	c.13+16340C>G		intron_variant		ENST00000637617.2	NP_001372910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXN	ENST00000637617.2	c.13+16340C>G		intron_variant		5	NM_001385981.1	ENSP00000489840.1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40521 AN: 151960 Hom.: 7815 Cov.: 31

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.267 AC: 40580 AN: 152078 Hom.: 7833 Cov.: 31 AF XY: 0.269 AC XY: 19977 AN XY: 74332

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.228

Alfa AF: 0.199 Hom.: 601

Bravo AF: 0.291

Asia WGS AF: 0.359 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.091
DANN	Benign	0.47

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: rs1634815; hg19: chr12-120687080;