chr10-101227346-G-T

Variant names:

• chr10-101227346-G-T
• rs756080073
• NM_006562.5:c.770C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006562.5(LBX1):​c.770C>A​(p.Pro257Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,368 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. P257L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LBX1 NM_006562.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.14
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34681824).

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.770C>A	p.Pro257Gln	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.770C>A	p.Pro257Gln	missense	Exon 2 of 2	ENSP00000359212.2	P52954
	LBX1	ENST00000945825.1		c.770C>A	p.Pro257Gln	missense	Exon 3 of 3	ENSP00000615884.1
	LBX1	ENST00000945826.1		c.770C>A	p.Pro257Gln	missense	Exon 3 of 3	ENSP00000615885.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 234902 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 AF: 6.87e-7 AC: 1 AN: 1456368 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724516

African (AFR) AF: 0.00 AC: 0 AN: 32962

American (AMR) AF: 0.00 AC: 0 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39402

South Asian (SAS) AF: 0.00 AC: 0 AN: 86108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5000

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110718

Other (OTH) AF: 0.00 AC: 0 AN: 60112

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.44	D
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.1
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.50	P
Vest4		0.37
MutPred		0.23		Loss of glycosylation at S256 (P = 0.0756)
MVP		0.84
ClinPred		0.94	D
GERP RS		3.9
Varity_R		0.28
gMVP		0.42
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs756080073; hg19: chr10-102987103;