10-101228650-C-G

Variant names:

• chr10-101228650-C-G
• rs779099123
• NM_006562.5:c.166G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006562.5(LBX1):​c.166G>C​(p.Ala56Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,442,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A56S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LBX1 NM_006562.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• Publications: 0 publications found

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]

LBX1-AS1 (HGNC:48678): (LBX1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2317963).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006562.5. 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
	LBX1	NM_006562.5	MANE Select	c.166G>C	p.Ala56Pro	missense	Exon 1 of 2	NP_006553.2	P52954

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBX1	ENST00000370193.4	TSL:1 MANE Select	c.166G>C	p.Ala56Pro	missense	Exon 1 of 2	ENSP00000359212.2	P52954
	LBX1	ENST00000945825.1		c.166G>C	p.Ala56Pro	missense	Exon 2 of 3	ENSP00000615884.1
	LBX1	ENST00000945826.1		c.166G>C	p.Ala56Pro	missense	Exon 2 of 3	ENSP00000615885.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1442988 Hom.: 0 Cov.: 32 AF XY: 0.00000279 AC XY: 2 AN XY: 716390

African (AFR) AF: 0.00 AC: 0 AN: 32128

American (AMR) AF: 0.00 AC: 0 AN: 41842

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25548

East Asian (EAS) AF: 0.00 AC: 0 AN: 38526

South Asian (SAS) AF: 0.00 AC: 0 AN: 83290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1104408

Other (OTH) AF: 0.0000168 AC: 1 AN: 59560

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	-0.11	N
PhyloP100		1.7
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	1.9	N
REVEL	Uncertain	0.37
Sift	Benign	0.59	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.38
MutPred		0.56		Loss of catalytic residue at A56 (P = 0.0336)
MVP		0.82
ClinPred		0.44	T
GERP RS		3.3
Varity_R		0.24
gMVP		0.70
Mutation Taster		=79/21	polymorphism

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

dbSNP: rs779099123; hg19: chr10-102988407;