rs864621969

Positions:

• chr9-126615549-C-G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001174147.2(LMX1B):​c.306C>G​(p.Tyr102Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LMX1B NM_001174147.2 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.47

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 Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-126615549-C-G is Pathogenic according to our data. Variant chr9-126615549-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 208164.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.306C>G	p.Tyr102Ter	stop_gained	2/8	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.306C>G	p.Tyr102Ter	stop_gained	2/8		NP_001167617.1
LMX1B	NM_002316.4	c.306C>G	p.Tyr102Ter	stop_gained	2/8		NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9	c.306C>G	p.Tyr102Ter	stop_gained	2/8	1	NM_001174147.2	ENSP00000362573	P4
LMX1B	ENST00000355497.10	c.306C>G	p.Tyr102Ter	stop_gained	2/8	1		ENSP00000347684
LMX1B	ENST00000526117.6	c.306C>G	p.Tyr102Ter	stop_gained	2/8	1		ENSP00000436930	A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nail-patella syndrome Pathogenic:1

Pathogenic, criteria provided, single submitter

research

Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília

Apr 01, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	42
DANN	Uncertain	1.0
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
MutationTaster	Benign	1.0	A;A;A;A;A
Vest4		0.79
GERP RS		4.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs864621969; hg19: chr9-129377828;