chr9-126695882-G-A

Variant names:

• chr9-126695882-G-A
• rs112171815
• NM_001174147.2:c.930G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001174147.2(LMX1B):​c.930G>A​(p.Thr310Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,613,184 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (76 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (51 hom.)
• Consequence: LMX1B NM_001174147.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.449
• 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: 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 9-126695882-G-A is Benign according to our data. Variant chr9-126695882-G-A is described in ClinVar as Benign. ClinVar VariationId is 258631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

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.930G>A	p.Thr310Thr	synonymous	Exon 7 of 8	NP_001167618.1
	LMX1B	NM_001174146.2		c.963G>A	p.Thr321Thr	synonymous	Exon 7 of 8	NP_001167617.1
	LMX1B	NM_002316.4		c.930G>A	p.Thr310Thr	synonymous	Exon 7 of 8	NP_002307.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1B	ENST00000373474.9	TSL:1 MANE Select	c.930G>A	p.Thr310Thr	synonymous	Exon 7 of 8	ENSP00000362573.3
	LMX1B	ENST00000355497.10	TSL:1	c.963G>A	p.Thr321Thr	synonymous	Exon 7 of 8	ENSP00000347684.5
	LMX1B	ENST00000526117.6	TSL:1	c.930G>A	p.Thr310Thr	synonymous	Exon 7 of 8	ENSP00000436930.1

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2353 AN: 151924 Hom.: 76 Cov.: 32

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00407 AC: 1004 AN: 246744 AF XY: 0.00286

Gnomad AFR exome AF: 0.0571

Gnomad AMR exome AF: 0.00177

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000909

Gnomad OTH exome AF: 0.00247

GnomAD4 exome AF: 0.00159 AC: 2324 AN: 1461142 Hom.: 51 Cov.: 33 AF XY: 0.00128 AC XY: 927 AN XY: 726922

African (AFR) AF: 0.0579 AC: 1940 AN: 33478

American (AMR) AF: 0.00266 AC: 119 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53012

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5742

European-Non Finnish (NFE) AF: 0.0000468 AC: 52 AN: 1111844

Other (OTH) AF: 0.00331 AC: 200 AN: 60356

GnomAD4 genome AF: 0.0155 AC: 2356 AN: 152042 Hom.: 76 Cov.: 32 AF XY: 0.0152 AC XY: 1127 AN XY: 74314

African (AFR) AF: 0.0538 AC: 2230 AN: 41436

American (AMR) AF: 0.00654 AC: 100 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67926

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00773 Hom.: 14

Bravo AF: 0.0181

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Focal segmental glomerulosclerosis (1)
-	-	1	Nail-patella syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	12
DANN	Benign	0.65
PhyloP100		-0.45
Mutation Taster		=83/17	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs112171815; hg19: chr9-129458161;