rs141161147

Variant names:

• chr10-101227296-C-A
• rs141161147
• NM_006562.5:c.820G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-101227296-C-A
• chr10-101227296-C-T

Variant summary

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

The NM_006562.5(LBX1):​c.820G>T​(p.Asp274Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,016 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D274N) 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: 1.47
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.820G>T	p.Asp274Tyr	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.820G>T	p.Asp274Tyr	missense	Exon 2 of 2	ENSP00000359212.2	P52954
	LBX1	ENST00000945825.1		c.820G>T	p.Asp274Tyr	missense	Exon 3 of 3	ENSP00000615884.1
	LBX1	ENST00000945826.1		c.820G>T	p.Asp274Tyr	missense	Exon 3 of 3	ENSP00000615885.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455016 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723886

African (AFR) AF: 0.00 AC: 0 AN: 32448

American (AMR) AF: 0.00 AC: 0 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25930

East Asian (EAS) AF: 0.00 AC: 0 AN: 38938

South Asian (SAS) AF: 0.00 AC: 0 AN: 86036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5178

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110174

Other (OTH) AF: 0.00 AC: 0 AN: 60046

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.75	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.5
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.36
MutPred		0.34		Gain of phosphorylation at D274 (P = 0.0089)
MVP		0.92
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.78
gMVP		0.51
Mutation Taster		=48/52	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

dbSNP: rs141161147; hg19: chr10-102987053;