chr11-58528135-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004811.3(LPXN):c.799T>C(p.Ser267Pro) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
LPXN
NM_004811.3 missense
NM_004811.3 missense
Scores
4
13
2
Clinical Significance
Conservation
PhyloP100: 2.98
Genes affected
LPXN (HGNC:14061): (leupaxin) The product encoded by this gene is preferentially expressed in hematopoietic cells and belongs to the paxillin protein family. Similar to other members of this focal-adhesion-associated adaptor-protein family, it has four leucine-rich LD-motifs in the N-terminus and four LIM domains in the C-terminus. It may function in cell type-specific signaling by associating with PYK2, a member of focal adhesion kinase family. As a substrate for a tyrosine kinase in lymphoid cells, this protein may also function in, and be regulated by, tyrosine kinase activity. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Jan 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.808
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LPXN | NM_004811.3 | c.799T>C | p.Ser267Pro | missense_variant | 8/9 | ENST00000395074.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LPXN | ENST00000395074.7 | c.799T>C | p.Ser267Pro | missense_variant | 8/9 | 1 | NM_004811.3 | A2 | |
LPXN | ENST00000530561.5 | c.*769T>C | 3_prime_UTR_variant, NMD_transcript_variant | 9/10 | 1 | ||||
LPXN | ENST00000528954.5 | c.814T>C | p.Ser272Pro | missense_variant | 8/9 | 2 | A2 | ||
LPXN | ENST00000528489.1 | c.739T>C | p.Ser247Pro | missense_variant | 7/8 | 2 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 05, 2023 | The c.814T>C (p.S272P) alteration is located in exon 8 (coding exon 8) of the LPXN gene. This alteration results from a T to C substitution at nucleotide position 814, causing the serine (S) at amino acid position 272 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.
REVEL
Pathogenic
Sift
Uncertain
D;D;.
Sift4G
Uncertain
D;D;D
Polyphen
P;.;P
Vest4
MutPred
Loss of ubiquitination at K269 (P = 0.0931);.;.;
MVP
MPC
0.56
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.