11-58551219-G-T

Position:

• chr11-58551219-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004811.3(LPXN):​c.332C>A​(p.Ala111Glu) 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. 14/21 in silico tools predict a benign 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0730

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060040772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPXN	NM_004811.3	c.332C>A	p.Ala111Glu	missense_variant	5/9	ENST00000395074.7	NP_004802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPXN	ENST00000395074.7	c.332C>A	p.Ala111Glu	missense_variant	5/9	1	NM_004811.3	ENSP00000378512.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 21, 2021

The c.347C>A (p.A116E) alteration is located in exon 5 (coding exon 5) of the LPXN gene. This alteration results from a C to A substitution at nucleotide position 347, causing the alanine (A) at amino acid position 116 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.036	T;.;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.56	T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.060	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N;N;.
REVEL	Benign	0.061
Sift	Benign	0.28	T;T;.
Sift4G	Benign	0.67	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.066
MutPred		0.30		Loss of MoRF binding (P = 0.0258);.;.;
MVP		0.55
MPC		0.17
ClinPred		0.12	T
GERP RS		2.7
Varity_R		0.058
gMVP		0.48

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-58318692;