rs770157240

Variant names:

• chr13-27550343-C-G
• NM_153371.4:c.1927G>C

Your query was ambiguous. Multiple possible variants found:

• chr13-27550343-C-G
• chr13-27550343-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_153371.4(LNX2):​c.1927G>C​(p.Gly643Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LNX2 NM_153371.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.14

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.892

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LNX2	NM_153371.4	c.1927G>C	p.Gly643Arg	missense_variant	Exon 9 of 10	ENST00000316334.5	NP_699202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LNX2	ENST00000316334.5	c.1927G>C	p.Gly643Arg	missense_variant	Exon 9 of 10	1	NM_153371.4	ENSP00000325929.3
LNX2	ENST00000649248.1	c.1927G>C	p.Gly643Arg	missense_variant	Exon 10 of 11			ENSP00000497224.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460262 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726466

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.17	T;T
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-5.8	D;.
REVEL	Uncertain	0.54
Sift	Benign	0.072	T;.
Sift4G	Benign	0.069	T;.
Polyphen		0.99	D;D
Vest4		0.75
MutPred		0.77		Gain of catalytic residue at A639 (P = 9e-04);Gain of catalytic residue at A639 (P = 9e-04);
MVP		0.81
MPC		1.4
ClinPred		1.0	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.50
gMVP		0.88

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: chr13-28124480;