4-53498696-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001126328.3(LNX1):​c.923G>A​(p.Arg308His) variant causes a missense change. The variant allele was found at a frequency of 0.0000793 in 1,614,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

LNX1
NM_001126328.3 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64
Variant links:
Genes affected
LNX1 (HGNC:6657): (ligand of numb-protein X 1) This gene encodes a membrane-bound protein that is involved in signal transduction and protein interactions. The encoded product is an E3 ubiquitin-protein ligase, which mediates ubiquitination and subsequent proteasomal degradation of proteins containing phosphotyrosine binding (PTB) domains. This protein may play an important role in tumorogenesis. Alternatively spliced transcript variants encoding distinct isoforms have been described. A pseudogene, which is located on chromosome 17, has been identified for this gene. [provided by RefSeq, Jul 2008]
LNX1-AS1 (HGNC:40345): (LNX1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.15043524).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LNX1NM_001126328.3 linkc.923G>A p.Arg308His missense_variant Exon 5 of 11 ENST00000263925.8 NP_001119800.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LNX1ENST00000263925.8 linkc.923G>A p.Arg308His missense_variant Exon 5 of 11 1 NM_001126328.3 ENSP00000263925.7 Q8TBB1-1
ENSG00000282278ENST00000507166.5 linkc.1017+72731C>T intron_variant Intron 12 of 23 2 ENSP00000423325.1 A0A0B4J203

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000139
AC:
35
AN:
251420
Hom.:
0
AF XY:
0.000147
AC XY:
20
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000173
Gnomad ASJ exome
AF:
0.000298
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000457
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000967
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000821
AC:
120
AN:
1461860
Hom.:
0
Cov.:
31
AF XY:
0.0000963
AC XY:
70
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.000230
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000475
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000432
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152266
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000966
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.000148
AC:
18
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000237

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.923G>A (p.R308H) alteration is located in exon 5 (coding exon 4) of the LNX1 gene. This alteration results from a G to A substitution at nucleotide position 923, causing the arginine (R) at amino acid position 308 to be replaced by a histidine (H). 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
0.079
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.49
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
.;T
Eigen
Benign
-0.071
Eigen_PC
Benign
-0.059
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
.;L
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.8
N;N
REVEL
Benign
0.10
Sift
Uncertain
0.010
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
0.86
P;P
Vest4
0.31
MVP
0.46
MPC
0.095
ClinPred
0.11
T
GERP RS
3.6
Varity_R
0.072
gMVP
0.44

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

LitVar

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

Other links and lift over

dbSNP: rs542109970; hg19: chr4-54364863; API