rs4767884

Positions:

• chr12-120224174-T-A
• chr12-120224174-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385981.1(PXN):​c.217A>T​(p.Ser73Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PXN NM_001385981.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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]

LOC124903034 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09579864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXN	NM_001385981.1	c.217A>T	p.Ser73Cys	missense_variant	2/15	ENST00000637617.2	NP_001372910.1
LOC124903034	XR_007063486.1	n.3695T>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXN	ENST00000637617.2	c.217A>T	p.Ser73Cys	missense_variant	2/15	5	NM_001385981.1	ENSP00000489840	A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1441978 Hom.: 0 Cov.: 50 AF XY: 0.00 AC XY: 0 AN XY: 715490

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.21	.;T;.;T;T;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.66	T;T;T;T;T;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.096	T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.1	L;L;L;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.78	N;N;N;N;.;N
REVEL	Benign	0.061
Sift	Benign	0.032	D;D;T;T;.;D
Sift4G	Benign	0.19	T;T;T;T;.;.
Polyphen		0.71, 0.41	.;P;B;.;.;.
Vest4		0.27
MutPred		0.33		Loss of phosphorylation at S73 (P = 0.0485);Loss of phosphorylation at S73 (P = 0.0485);Loss of phosphorylation at S73 (P = 0.0485);.;Loss of phosphorylation at S73 (P = 0.0485);.;
MVP		0.56
MPC		0.17
ClinPred		0.13	T
GERP RS		0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.054
gMVP		0.18

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: rs4767884; hg19: chr12-120661977;