13-27562759-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153371.4(LNX2):c.878A>G(p.Asn293Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000617 in 1,459,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: LNX2 NM_153371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.93

Genes affected

LNX2 (HGNC:20421): (ligand of numb-protein X 2) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in protein ubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.19490966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LNX2	NM_153371.4	c.878A>G	p.Asn293Ser	missense_variant	5/10	ENST00000316334.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LNX2	ENST00000316334.5	c.878A>G	p.Asn293Ser	missense_variant	5/10	1	NM_153371.4	P1
LNX2	ENST00000649248.1	c.878A>G	p.Asn293Ser	missense_variant	6/11			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000617 AC: 9 AN: 1459052 Hom.: 0 Cov.: 32 AF XY: 0.00000414 AC XY: 3 AN XY: 725304

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000811

Gnomad4 OTH exome AF: 0.00

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

Feb 05, 2024

The c.878A>G (p.N293S) alteration is located in exon 5 (coding exon 4) of the LNX2 gene. This alteration results from a A to G substitution at nucleotide position 878, causing the asparagine (N) at amino acid position 293 to be replaced by a serine (S). 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	0.062
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	19
Dann	Uncertain	0.98
DEOGEN2	Benign	0.055	T;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.019
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.96	L;L
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Benign	0.069
Sift	Benign	0.30	T;.
Sift4G	Benign	0.44	T;.
Polyphen		0.0030	B;B
Vest4		0.31
MutPred		0.56		Gain of catalytic residue at N293 (P = 5e-04);Gain of catalytic residue at N293 (P = 5e-04);
MVP		0.53
MPC		0.043
ClinPred		0.72	D
GERP RS		4.7
Varity_R		0.13
gMVP		0.34

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-28136896;