9-126693308-G-T

Variant names:

• chr9-126693308-G-T
• NM_001174147.2:c.726G>T
• LMX1B p.Ser242Ser

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001174147.2(LMX1B):​c.726G>T​(p.Ser242Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S242S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LMX1B NM_001174147.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 0 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: G2P, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• nail-patella-like renal disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=0.205 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174147.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1B	NM_001174147.2	MANE Select	c.726G>T	p.Ser242Ser	synonymous	Exon 4 of 8	NP_001167618.1	O60663-1
	LMX1B	NM_001174146.2		c.726G>T	p.Ser242Ser	synonymous	Exon 4 of 8	NP_001167617.1	O60663-3
	LMX1B	NM_002316.4		c.726G>T	p.Ser242Ser	synonymous	Exon 4 of 8	NP_002307.2	O60663-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1B	ENST00000373474.9	TSL:1 MANE Select	c.726G>T	p.Ser242Ser	synonymous	Exon 4 of 8	ENSP00000362573.3	O60663-1
	LMX1B	ENST00000355497.10	TSL:1	c.726G>T	p.Ser242Ser	synonymous	Exon 4 of 8	ENSP00000347684.5	O60663-3
	LMX1B	ENST00000526117.6	TSL:1	c.726G>T	p.Ser242Ser	synonymous	Exon 4 of 8	ENSP00000436930.1	O60663-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1448190 Hom.: 0 Cov.: 51 AF XY: 0.00 AC XY: 0 AN XY: 719530

African (AFR) AF: 0.00 AC: 0 AN: 33074

American (AMR) AF: 0.00 AC: 0 AN: 42918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25862

East Asian (EAS) AF: 0.00 AC: 0 AN: 38838

South Asian (SAS) AF: 0.00 AC: 0 AN: 84432

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4642

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106222

Other (OTH) AF: 0.00 AC: 0 AN: 59766

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	10
DANN	Benign	0.51
PhyloP100		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-129455587;