rs1554728691

Variant names:

• chr9-126693292-CCTT-C
• rs1554728691
• NM_001174147.2:c.712_714delTTC

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM1 PM2 PM4_Supporting

The NM_001174147.2(LMX1B):​c.712_714delTTC​(p.Phe238del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. F238F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LMX1B NM_001174147.2 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.61
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• nail-patella syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P
• nail-patella-like renal disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM1: In a hotspot region, there are 6 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 6 uncertain in NM_001174147.2
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001174147.2. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.712_714delTTC	p.Phe238del	conservative_inframe_deletion	Exon 4 of 8	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.712_714delTTC	p.Phe238del	conservative_inframe_deletion	Exon 4 of 8		NP_001167617.1
LMX1B	NM_002316.4	c.712_714delTTC	p.Phe238del	conservative_inframe_deletion	Exon 4 of 8		NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9	c.712_714delTTC	p.Phe238del	conservative_inframe_deletion	Exon 4 of 8	1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.712_714delTTC	p.Phe238del	conservative_inframe_deletion	Exon 4 of 8	1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.712_714delTTC	p.Phe238del	conservative_inframe_deletion	Exon 4 of 8	1		ENSP00000436930.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jun 15, 2017

Ambry 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
PhyloP100		7.6
Mutation Taster		=1/99	disease causing

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

Other links and lift over

dbSNP: rs1554728691; hg19: chr9-129455571;