Variant 11-58528197-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004811.3(LPXN):c.743-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00741 in 1,612,922 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 56 hom. )

Consequence

LPXN
NM_004811.3 splice_region, intron

Scores

Splicing: ADA: 0.00009801

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.315

Variant links:

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]

LPXN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 11-58528197-G-A is Benign according to our data. Variant chr11-58528197-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2641805.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPXN	NM_004811.3 link	c.743-6C>T		splice_region_variant, intron_variant		ENST00000395074.7	NP_004802.1	O60711-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
LPXN	ENST00000395074.7 link	c.743-6C>T	splice_region_variant, intron_variant	1	NM_004811.3	ENSP00000378512.2	O60711-1
LPXN	ENST00000530561.5 link	n.*713-6C>T	splice_region_variant, intron_variant	1		ENSP00000437094.1	E9PNX9
LPXN	ENST00000528954.5 link	c.758-6C>T	splice_region_variant, intron_variant	2		ENSP00000431284.1	O60711-2
LPXN	ENST00000528489.1 link	c.683-6C>T	splice_region_variant, intron_variant	2		ENSP00000461855.1	B7Z5P7

Frequencies

GnomAD3 genomes

AF:

0.00519

AC:

790

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0103

Gnomad FIN

AF:

0.00367

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00811

Gnomad OTH

AF:

0.00672

GnomAD3 exomes

AF:

0.00573

AC:

1437

AN:

250860

Hom.:

AF XY:

0.00585

AC XY:

793

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.00538

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00789

Gnomad FIN exome

AF:

0.00430

Gnomad NFE exome

AF:

0.00756

Gnomad OTH exome

AF:

0.00670

GnomAD4 exome

AF:

0.00764

AC:

11161

AN:

1460624

Hom.:

Cov.:

AF XY:

0.00776

AC XY:

5638

AN XY:

726372

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00345

Gnomad4 ASJ exome

AF:

0.00636

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00786

Gnomad4 FIN exome

AF:

0.00425

Gnomad4 NFE exome

AF:

0.00850

Gnomad4 OTH exome

AF:

0.00719

GnomAD4 genome

AF:

0.00518

AC:

789

AN:

152298

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

359

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0101

Gnomad4 FIN

AF:

0.00367

Gnomad4 NFE

AF:

0.00811

Gnomad4 OTH

AF:

0.00665

Alfa

AF:

0.00666

Hom.:

Bravo

AF:

0.00468

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00693

EpiControl

AF:

0.00652

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

LPXN: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.1

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000098

dbscSNV1_RF

Benign

0.0060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over