9-126614529-G-A

Position:

• chr9-126614529-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001174147.2(LMX1B):​c.80G>A​(p.Gly27Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,454,010 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LMX1B NM_001174147.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.44

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.80G>A	p.Gly27Asp	missense_variant	1/8	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.80G>A	p.Gly27Asp	missense_variant	1/8		NP_001167617.1
LMX1B	NM_002316.4	c.80G>A	p.Gly27Asp	missense_variant	1/8		NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9	c.80G>A	p.Gly27Asp	missense_variant	1/8	1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.80G>A	p.Gly27Asp	missense_variant	1/8	1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.80G>A	p.Gly27Asp	missense_variant	1/8	1		ENSP00000436930.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1454010 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722840

Gnomad4 AFR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ExAC AF: 0.0000166 AC: 2

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

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 20, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	.;T;.;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.015
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Pathogenic	0.57	D
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.34	N;N;N;.
PrimateAI	Pathogenic	0.98	D
PROVEAN	Benign	-0.39	N;N;N;N
REVEL	Uncertain	0.31
Sift	Benign	0.12	T;T;T;T
Sift4G	Uncertain	0.034	D;D;D;D
Polyphen		0.0020	.;.;.;B
Vest4		0.61
MVP		0.53
MPC		0.95
ClinPred		0.39	T
GERP RS		3.0
Varity_R		0.23
gMVP		0.58

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: rs771325027; hg19: chr9-129376808;