chr13-27550433-A-G

Variant names:

• chr13-27550433-A-G
• NM_153371.4:c.1837T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_153371.4(LNX2):​c.1837T>C​(p.Phe613Leu) 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 pathogenic 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: 9.28
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153371.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNX2	NM_153371.4	MANE Select	c.1837T>C	p.Phe613Leu	missense	Exon 9 of 10	NP_699202.1	Q8N448

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNX2	ENST00000316334.5	TSL:1 MANE Select	c.1837T>C	p.Phe613Leu	missense	Exon 9 of 10	ENSP00000325929.3	Q8N448
	LNX2	ENST00000649248.1		c.1837T>C	p.Phe613Leu	missense	Exon 10 of 11	ENSP00000497224.1	Q8N448
	LNX2	ENST00000869675.1		c.1837T>C	p.Phe613Leu	missense	Exon 9 of 10	ENSP00000539734.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.025	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.7	L
PhyloP100		9.3
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.55
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.91
MutPred		0.59		Gain of catalytic residue at S610 (P = 5e-04)
MVP		0.69
MPC		1.4
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.86
gMVP		0.75
Mutation Taster		=27/73	disease causing

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

hg19: chr13-28124570;