NM_001126328.3:c.380+24352G>T

Variant names:

• chr4-53549271-C-A
• rs2280119
• NM_001126328.3:c.380+24352G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001126328.3(LNX1):​c.380+24352G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 151,894 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000020 (0 hom., cov: 31)
• Consequence: LNX1 NM_001126328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762
• Publications: 2 publications found

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]

ENSG00000282278 (HGNC:):

LNX1-AS1 (HGNC:40345): (LNX1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126328.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNX1	NM_001126328.3	MANE Select	c.380+24352G>T		intron	N/A	NP_001119800.1
	LNX1	NM_032622.3		c.92+8603G>T		intron	N/A	NP_116011.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNX1	ENST00000263925.8	TSL:1 MANE Select	c.380+24352G>T		intron	N/A	ENSP00000263925.7
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1017+123306C>A		intron	N/A	ENSP00000423325.1
	LNX1	ENST00000306888.6	TSL:1	c.92+8603G>T		intron	N/A	ENSP00000302879.2

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151894 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151894 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 74174

African (AFR) AF: 0.0000725 AC: 3 AN: 41356

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 305

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.36
PhyloP100		-0.76

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: rs2280119; hg19: chr4-54415438;