chr13-27562414-T-C

Position:

• chr13-27562414-T-C

Variant summary

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

The NM_153371.4(LNX2):​c.1223A>G​(p.Gln408Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LNX2 NM_153371.4 missense, splice_region
• Scores: Splicing: ADA: 0.9983
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

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/exons	MANE	UniProt
LNX2	NM_153371.4	c.1223A>G	p.Gln408Arg	missense_variant, splice_region_variant	5/10	ENST00000316334.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LNX2	ENST00000316334.5	c.1223A>G	p.Gln408Arg	missense_variant, splice_region_variant	5/10	1	NM_153371.4	P1
LNX2	ENST00000649248.1	c.1223A>G	p.Gln408Arg	missense_variant, splice_region_variant	6/11			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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 27, 2022

The c.1223A>G (p.Q408R) 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 1223, causing the glutamine (Q) at amino acid position 408 to be replaced by an arginine (R). 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	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.96	L;L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.0	N;.
REVEL	Uncertain	0.31
Sift	Uncertain	0.0080	D;.
Sift4G	Uncertain	0.011	D;.
Polyphen		0.85	P;P
Vest4		0.87
MutPred		0.43		Gain of catalytic residue at Q408 (P = 0.007);Gain of catalytic residue at Q408 (P = 0.007);
MVP		0.66
MPC		0.28
ClinPred		0.91	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.46
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.93
SpliceAI score (max)		0.070		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: chr13-28136551;