9-126693308-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001174147.2(LMX1B):​c.726G>C​(p.Ser242Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,599,944 control chromosomes in the GnomAD database, including 144,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13525 hom., cov: 33)
  • Exomes 𝑓: 0.42 (130665 hom.)
• Consequence: LMX1B NM_001174147.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11 O:1
• 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, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• nail-patella-like renal disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 9-126693308-G-C is Benign according to our data. Variant chr9-126693308-G-C is described in ClinVar as Benign. ClinVar VariationId is 258629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.205 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 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.726G>C	p.Ser242Ser	synonymous	Exon 4 of 8	NP_001167618.1	O60663-1
	LMX1B	NM_001174146.2		c.726G>C	p.Ser242Ser	synonymous	Exon 4 of 8	NP_001167617.1	O60663-3
	LMX1B	NM_002316.4		c.726G>C	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>C	p.Ser242Ser	synonymous	Exon 4 of 8	ENSP00000362573.3	O60663-1
	LMX1B	ENST00000355497.10	TSL:1	c.726G>C	p.Ser242Ser	synonymous	Exon 4 of 8	ENSP00000347684.5	O60663-3
	LMX1B	ENST00000526117.6	TSL:1	c.726G>C	p.Ser242Ser	synonymous	Exon 4 of 8	ENSP00000436930.1	O60663-2

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63677 AN: 151986 Hom.: 13509 Cov.: 33

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.421

GnomAD2 exomes AF: 0.435 AC: 98320 AN: 226044 AF XY: 0.434

Gnomad AFR exome AF: 0.396

Gnomad AMR exome AF: 0.443

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.554

Gnomad FIN exome AF: 0.392

Gnomad NFE exome AF: 0.426

Gnomad OTH exome AF: 0.422

GnomAD4 exome AF: 0.423 AC: 612814 AN: 1447840 Hom.: 130665 Cov.: 51 AF XY: 0.424 AC XY: 304814 AN XY: 719362

African (AFR) AF: 0.388 AC: 12830 AN: 33064

American (AMR) AF: 0.438 AC: 18767 AN: 42890

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 11434 AN: 25862

East Asian (EAS) AF: 0.524 AC: 20353 AN: 38820

South Asian (SAS) AF: 0.431 AC: 36390 AN: 84402

European-Finnish (FIN) AF: 0.394 AC: 20661 AN: 52432

Middle Eastern (MID) AF: 0.435 AC: 2019 AN: 4640

European-Non Finnish (NFE) AF: 0.420 AC: 464753 AN: 1105978

Other (OTH) AF: 0.429 AC: 25607 AN: 59752

GnomAD4 genome AF: 0.419 AC: 63731 AN: 152104 Hom.: 13525 Cov.: 33 AF XY: 0.418 AC XY: 31082 AN XY: 74362

African (AFR) AF: 0.395 AC: 16378 AN: 41510

American (AMR) AF: 0.426 AC: 6509 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1518 AN: 3468

East Asian (EAS) AF: 0.541 AC: 2773 AN: 5128

South Asian (SAS) AF: 0.422 AC: 2039 AN: 4828

European-Finnish (FIN) AF: 0.390 AC: 4133 AN: 10590

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28977 AN: 67974

Other (OTH) AF: 0.417 AC: 879 AN: 2110

Alfa AF: 0.384 Hom.: 3510

Bravo AF: 0.421

Asia WGS AF: 0.441 AC: 1534 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	not provided (3)
-	-	2	Nail-patella syndrome (3)
-	-	1	Nail-patella-like renal disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.6
DANN	Benign	0.54
PhyloP100		0.20
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13295990; hg19: chr9-129455587; COSMIC: COSV62739189;