chr9-126614536-G-T

Variant names:

• chr9-126614536-G-T
• rs1244659568
• NM_001174147.2:c.87G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001174147.2(LMX1B):​c.87G>T​(p.Lys29Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LMX1B NM_001174147.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.948

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39348203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.87G>T	p.Lys29Asn	missense_variant	Exon 1 of 8	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.87G>T	p.Lys29Asn	missense_variant	Exon 1 of 8		NP_001167617.1
LMX1B	NM_002316.4	c.87G>T	p.Lys29Asn	missense_variant	Exon 1 of 8		NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9	c.87G>T	p.Lys29Asn	missense_variant	Exon 1 of 8	1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.87G>T	p.Lys29Asn	missense_variant	Exon 1 of 8	1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.87G>T	p.Lys29Asn	missense_variant	Exon 1 of 8	1		ENSP00000436930.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.00000870 AC: 2 AN: 229988 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 126102

Gnomad AFR exome AF: 0.000141

Gnomad AMR exome AF: 0.00

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: 6.88e-7 AC: 1 AN: 1454064 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722912

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

Bravo AF: 0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nail-patella syndrome;C0403548:Nail-patella-like renal disease Uncertain:1

Jan 08, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	.;D;.;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.069
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Pathogenic	0.80	D
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Uncertain	-0.088	T
MutationAssessor	Benign	0.55	N;N;N;.
PrimateAI	Pathogenic	0.97	D
PROVEAN	Benign	-0.84	N;N;N;N
REVEL	Uncertain	0.39
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.034	D;D;D;D
Polyphen		1.0	.;.;.;D
Vest4		0.39
MVP		0.53
MPC		1.9
ClinPred		0.58	D
GERP RS		2.1
Varity_R		0.41
gMVP		0.73

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

Other links and lift over

dbSNP: rs1244659568; hg19: chr9-129376815;