13-27553252-A-C

Position:

• chr13-27553252-A-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.1734T>G​(p.Asp578Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: LNX2 NM_153371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.144

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=0.091656625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LNX2	NM_153371.4	c.1734T>G	p.Asp578Glu	missense_variant	8/10	ENST00000316334.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LNX2	ENST00000316334.5	c.1734T>G	p.Asp578Glu	missense_variant	8/10	1	NM_153371.4	P1
LNX2	ENST00000649248.1	c.1734T>G	p.Asp578Glu	missense_variant	9/11			P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 19, 2023

The c.1734T>G (p.D578E) alteration is located in exon 8 (coding exon 7) of the LNX2 gene. This alteration results from a T to G substitution at nucleotide position 1734, causing the aspartic acid (D) at amino acid position 578 to be replaced by a glutamic acid (E). 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	0.24
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.0
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0093	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.67	.;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.092	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	0.93	D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.34	N;.
REVEL	Benign	0.27
Sift	Benign	0.16	T;.
Sift4G	Benign	0.43	T;.
Polyphen		0.032	B;B
Vest4		0.56
MutPred		0.40		Gain of disorder (P = 0.0909);Gain of disorder (P = 0.0909);
MVP		0.19
MPC		1.2
ClinPred		0.20	T
GERP RS		-12
Varity_R		0.094
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-28127389;