10-101228674-G-C

Variant names:

• chr10-101228674-G-C
• NM_006562.5:c.142C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006562.5(LBX1):​c.142C>G​(p.Arg48Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LBX1 NM_006562.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06

Genes affected

LBX1 (HGNC:16960): (ladybird homeobox 1) This gene and the orthologous mouse gene were found by their homology to the Drosophila lady bird early and late homeobox genes. In the mouse, this gene is a key regulator of muscle precursor cell migration and is required for the acquisition of dorsal identities of forelimb muscles. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41637412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBX1	NM_006562.5	c.142C>G	p.Arg48Gly	missense_variant	Exon 1 of 2	ENST00000370193.4	NP_006553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LBX1	ENST00000370193.4	c.142C>G	p.Arg48Gly	missense_variant	Exon 1 of 2	1	NM_006562.5	ENSP00000359212.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.142C>G (p.R48G) alteration is located in exon 1 (coding exon 1) of the LBX1 gene. This alteration results from a C to G substitution at nucleotide position 142, causing the arginine (R) at amino acid position 48 to be replaced by a glycine (G). 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	Uncertain	0.56
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.77	D
MetaRNN	Benign	0.42	T
MetaSVM	Uncertain	-0.029	T
MutationAssessor	Benign	2.0	M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.45
Sift	Uncertain	0.012	D
Sift4G	Benign	0.21	T
Polyphen		0.32	B
Vest4		0.38
MutPred		0.44		Gain of ubiquitination at K44 (P = 0.0766);
MVP		0.88
ClinPred		0.80	D
GERP RS		2.3
Varity_R		0.21
gMVP		0.48

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: chr10-102988431;