rs1634815

Variant names:

• chr12-120249277-G-C
• rs1634815
• NM_001385981.1:c.13+16340C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-120249277-G-C
• chr12-120249277-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PXN	NM_001385981.1	c.13+16340C>G		intron_variant	Intron 1 of 14	ENST00000637617.2	NP_001372910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PXN	ENST00000637617.2	c.13+16340C>G		intron_variant	Intron 1 of 14	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

African (AFR) AF: 0.518 AC: 21467 AN: 41450

American (AMR) AF: 0.263 AC: 4021 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 505 AN: 3472

East Asian (EAS) AF: 0.554 AC: 2862 AN: 5170

South Asian (SAS) AF: 0.231 AC: 1112 AN: 4822

European-Finnish (FIN) AF: 0.166 AC: 1753 AN: 10566

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8243 AN: 68010

Other (OTH) AF: 0.228 AC: 480 AN: 2108

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
PhyloP100		-4.2
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: rs1634815; hg19: chr12-120687080;