NM_001385981.1:c.2991G>A

Variant names:

• chr12-120212569-C-T
• rs25663
• NM_001385981.1:c.2991G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001385981.1(PXN):​c.2991G>A​(p.Thr997Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,611,694 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0062 (13 hom., cov: 33)
  • Exomes 𝑓: 0.00069 (16 hom.)
• Consequence: PXN NM_001385981.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.83
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 12-120212569-C-T is Benign according to our data. Variant chr12-120212569-C-T is described in ClinVar as Benign. ClinVar VariationId is 715656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.83 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00621 (946/152248) while in subpopulation AFR AF = 0.0214 (889/41544). AF 95% confidence interval is 0.0202. There are 13 homozygotes in GnomAd4. There are 461 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 946 AD gene.

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.2991G>A	p.Thr997Thr	synonymous	Exon 15 of 15	NP_001372910.1	A0A1B0GTU4
	PXN	NM_001385982.1		c.2715G>A	p.Thr905Thr	synonymous	Exon 14 of 14	NP_001372911.1
	PXN	NM_001385983.1		c.2709G>A	p.Thr903Thr	synonymous	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.2991G>A	p.Thr997Thr	synonymous	Exon 15 of 15	ENSP00000489840.1	A0A1B0GTU4
	PXN	ENST00000228307.11	TSL:1	c.1521G>A	p.Thr507Thr	synonymous	Exon 12 of 12	ENSP00000228307.7	P49023-1
	PXN	ENST00000424649.6	TSL:1	c.1419G>A	p.Thr473Thr	synonymous	Exon 11 of 11	ENSP00000391283.2	P49023-2

Frequencies

GnomAD3 genomes AF: 0.00622 AC: 946 AN: 152130 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00166 AC: 408 AN: 245240 AF XY: 0.00124

Gnomad AFR exome AF: 0.0234

Gnomad AMR exome AF: 0.000957

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000365

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.000685 AC: 1000 AN: 1459446 Hom.: 16 Cov.: 31 AF XY: 0.000575 AC XY: 417 AN XY: 725636

African (AFR) AF: 0.0245 AC: 821 AN: 33456

American (AMR) AF: 0.00128 AC: 57 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39644

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86222

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52918

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5754

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1110366

Other (OTH) AF: 0.00144 AC: 87 AN: 60286

GnomAD4 genome AF: 0.00621 AC: 946 AN: 152248 Hom.: 13 Cov.: 33 AF XY: 0.00619 AC XY: 461 AN XY: 74422

African (AFR) AF: 0.0214 AC: 889 AN: 41544

American (AMR) AF: 0.00288 AC: 44 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00354 Hom.: 4

Bravo AF: 0.00768

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.3
DANN	Benign	0.84
PhyloP100		-1.8
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs25663; hg19: chr12-120650372;