NM_006562.5:c.722C>T

Variant names:

• chr10-101227394-G-A
• rs768329748
• NM_006562.5:c.722C>T

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.722C>T​(p.Ala241Val) 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. 14/22 in silico tools predict 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. A241S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LBX1 NM_006562.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.829
• 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=0.102759).

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.722C>T	p.Ala241Val	missense	Exon 2 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.722C>T	p.Ala241Val	missense	Exon 2 of 2	ENSP00000359212.2	P52954
	LBX1	ENST00000945825.1		c.722C>T	p.Ala241Val	missense	Exon 3 of 3	ENSP00000615884.1
	LBX1	ENST00000945826.1		c.722C>T	p.Ala241Val	missense	Exon 3 of 3	ENSP00000615885.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 222418 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.22
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.10	T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.83
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.15
Sift	Benign	0.036	D
Sift4G	Benign	0.11	T
Polyphen		0.0010	B
Vest4		0.089
MutPred		0.17		Loss of glycosylation at P239 (P = 0.0732)
MVP		0.75
ClinPred		0.11	T
GERP RS		3.3
Varity_R		0.098
gMVP		0.20
Mutation Taster		=95/5	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: rs768329748; hg19: chr10-102987151;