rs4767884

Variant names:

• chr12-120224174-T-A
• rs4767884
• ENST00000458477.6:c.-183A>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025157.5(PXN):​c.-183A>T variant causes a 5 prime UTR premature start codon gain 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. 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_025157.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 42 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]

LOC124903034 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025157.5. 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.217A>T	p.Ser73Cys	missense	Exon 2 of 15	NP_001372910.1	A0A1B0GTU4
	PXN	NM_025157.5		c.-183A>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	NP_079433.3
	PXN	NM_001385982.1		c.217A>T	p.Ser73Cys	missense	Exon 2 of 14	NP_001372911.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXN	ENST00000458477.6	TSL:1	c.-183A>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	ENSP00000395536.2	P49023-4
	PXN	ENST00000637617.2	TSL:5 MANE Select	c.217A>T	p.Ser73Cys	missense	Exon 2 of 15	ENSP00000489840.1	A0A1B0GTU4
	PXN	ENST00000228307.11	TSL:1	c.217A>T	p.Ser73Cys	missense	Exon 2 of 12	ENSP00000228307.7	P49023-1

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

African (AFR) AF: 0.00 AC: 0 AN: 33210

American (AMR) AF: 0.00 AC: 0 AN: 41212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25470

East Asian (EAS) AF: 0.00 AC: 0 AN: 38950

South Asian (SAS) AF: 0.00 AC: 0 AN: 84072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102024

Other (OTH) AF: 0.00 AC: 0 AN: 59650

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.078
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.061
Sift	Benign	0.032	D
Sift4G	Benign	0.19	T
Polyphen		0.71	P
Vest4		0.27
MutPred		0.33		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
Mutation Taster		=300/0	polymorphism

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: rs4767884; hg19: chr12-120661977;