rs13295990

Variant names:

• chr9-126693308-G-A
• rs13295990
• NM_001174147.2:c.726G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-126693308-G-A
• chr9-126693308-G-C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_001174147.2(LMX1B):​c.726G>A​(p.Ser242Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,600,244 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: LMX1B NM_001174147.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 19 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=0.205 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000329 (5/152054) while in subpopulation AMR AF = 0.000262 (4/15280). AF 95% confidence interval is 0.0000888. There are 0 homozygotes in GnomAd4. There are 2 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.726G>A	p.Ser242Ser	synonymous_variant	Exon 4 of 8	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.726G>A	p.Ser242Ser	synonymous_variant	Exon 4 of 8		NP_001167617.1
LMX1B	NM_002316.4	c.726G>A	p.Ser242Ser	synonymous_variant	Exon 4 of 8		NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9	c.726G>A	p.Ser242Ser	synonymous_variant	Exon 4 of 8	1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.726G>A	p.Ser242Ser	synonymous_variant	Exon 4 of 8	1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.726G>A	p.Ser242Ser	synonymous_variant	Exon 4 of 8	1		ENSP00000436930.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152054 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00000442 AC: 1 AN: 226044 AF XY: 0.00000816

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000166 AC: 24 AN: 1448190 Hom.: 0 Cov.: 51 AF XY: 0.0000222 AC XY: 16 AN XY: 719530

African (AFR) AF: 0.0000302 AC: 1 AN: 33074

American (AMR) AF: 0.0000466 AC: 2 AN: 42918

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

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38838

South Asian (SAS) AF: 0.0000118 AC: 1 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: 0.0000163 AC: 18 AN: 1106222

Other (OTH) AF: 0.0000167 AC: 1 AN: 59766

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152054 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74276

African (AFR) AF: 0.00 AC: 0 AN: 41414

American (AMR) AF: 0.000262 AC: 4 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.00 Hom.: 3510

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs13295990; hg19: chr9-129455587;