Variant 9-126690941-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001174147.2(LMX1B):c.432C>G(p.Cys144Trp) 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 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LMX1B
NM_001174147.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0580

Variant links:

Genes affected

LMX1B (HGNC:6654): (LIM homeobox transcription factor 1 beta) This gene encodes a member of LIM-homeodomain family of proteins containing two N-terminal zinc-binding LIM domains, 1 homeodomain, and a C-terminal glutamine-rich domain. It functions as a transcription factor, and is essential for the normal development of dorsal limb structures, the glomerular basement membrane, the anterior segment of the eye, and dopaminergic and serotonergic neurons. Mutations in this gene are associated with nail-patella syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

LMX1B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.901

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMX1B	NM_001174147.2 linkuse as main transcript	c.432C>G	p.Cys144Trp	missense_variant	3/8	ENST00000373474.9	NP_001167618.1	O60663-1Q6ISE0
LMX1B	NM_001174146.2 linkuse as main transcript	c.432C>G	p.Cys144Trp	missense_variant	3/8		NP_001167617.1	B7ZLH2
LMX1B	NM_002316.4 linkuse as main transcript	c.432C>G	p.Cys144Trp	missense_variant	3/8		NP_002307.2	O60663-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LMX1B	ENST00000373474.9 linkuse as main transcript	c.432C>G	p.Cys144Trp	missense_variant	3/8	1	NM_001174147.2	ENSP00000362573.3	O60663-1
LMX1B	ENST00000355497.10 linkuse as main transcript	c.432C>G	p.Cys144Trp	missense_variant	3/8	1		ENSP00000347684.5	O60663-3
LMX1B	ENST00000526117.6 linkuse as main transcript	c.432C>G	p.Cys144Trp	missense_variant	3/8	1		ENSP00000436930.1	O60663-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250840

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000137

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.26

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.86

.;D;.;D

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Pathogenic

0.36

MetaRNN

Pathogenic

0.90

D;D;D;D

MetaSVM

Uncertain

0.34

MutationAssessor

Uncertain

2.5

M;M;M;.

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-5.2

D;D;D;D

REVEL

Pathogenic

0.71

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Uncertain

0.042

D;D;D;D

Polyphen

1.0

.;.;.;D

Vest4

0.86

MVP

0.99

MPC

2.1

ClinPred

0.99

GERP RS

2.0

Varity_R

0.73

gMVP

0.91

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over