NM_153371.4:c.1736C>T

Variant names:

• chr13-27553250-G-A
• NM_153371.4:c.1736C>T

Variant summary

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

The NM_153371.4(LNX2):​c.1736C>T​(p.Ala579Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LNX2 NM_153371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.65

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LNX2	NM_153371.4	c.1736C>T	p.Ala579Val	missense_variant	Exon 8 of 10	ENST00000316334.5	NP_699202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LNX2	ENST00000316334.5	c.1736C>T	p.Ala579Val	missense_variant	Exon 8 of 10	1	NM_153371.4	ENSP00000325929.3
LNX2	ENST00000649248.1	c.1736C>T	p.Ala579Val	missense_variant	Exon 9 of 11			ENSP00000497224.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1736C>T (p.A579V) alteration is located in exon 8 (coding exon 7) of the LNX2 gene. This alteration results from a C to T substitution at nucleotide position 1736, causing the alanine (A) at amino acid position 579 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.77	.;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.3	N;.
REVEL	Benign	0.20
Sift	Benign	0.12	T;.
Sift4G	Benign	0.13	T;.
Polyphen		0.077	B;B
Vest4		0.46
MutPred		0.37		Gain of catalytic residue at E576 (P = 0.044);Gain of catalytic residue at E576 (P = 0.044);
MVP		0.54
MPC		0.65
ClinPred		0.92	D
GERP RS		6.0
Varity_R		0.11
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: 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: chr13-28127387; COSMIC: COSV60337201;