9-126696349-C-T

Variant names:

• chr9-126696349-C-T
• rs10115304
• NM_001174147.2:c.1107C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The ENST00000373474.9(LMX1B):​c.1107C>T​(p.Ser369Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00932 in 1,614,024 control chromosomes in the GnomAD database, including 1,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (669 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (590 hom.)
• Consequence: LMX1B ENST00000373474.9 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.195
• Publications: 3 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 9-126696349-C-T is Benign according to our data. Variant chr9-126696349-C-T is described in ClinVar as Benign. ClinVar VariationId is 258620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.195 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000373474.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1B	NM_001174147.2	MANE Select	c.1107C>T	p.Ser369Ser	synonymous	Exon 8 of 8	NP_001167618.1
	LMX1B	NM_001174146.2		c.1119C>T	p.Ser373Ser	synonymous	Exon 8 of 8	NP_001167617.1
	LMX1B	NM_002316.4		c.1086C>T	p.Ser362Ser	synonymous	Exon 8 of 8	NP_002307.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1B	ENST00000373474.9	TSL:1 MANE Select	c.1107C>T	p.Ser369Ser	synonymous	Exon 8 of 8	ENSP00000362573.3
	LMX1B	ENST00000355497.10	TSL:1	c.1119C>T	p.Ser373Ser	synonymous	Exon 8 of 8	ENSP00000347684.5
	LMX1B	ENST00000526117.6	TSL:1	c.1086C>T	p.Ser362Ser	synonymous	Exon 8 of 8	ENSP00000436930.1

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7524 AN: 152132 Hom.: 665 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0359

GnomAD2 exomes AF: 0.0132 AC: 3328 AN: 251328 AF XY: 0.00967

Gnomad AFR exome AF: 0.181

Gnomad AMR exome AF: 0.00903

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000308

Gnomad OTH exome AF: 0.00570

GnomAD4 exome AF: 0.00513 AC: 7494 AN: 1461774 Hom.: 590 Cov.: 32 AF XY: 0.00443 AC XY: 3219 AN XY: 727210

African (AFR) AF: 0.181 AC: 6061 AN: 33472

American (AMR) AF: 0.0101 AC: 453 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000591 AC: 51 AN: 86254

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53394

Middle Eastern (MID) AF: 0.0120 AC: 69 AN: 5766

European-Non Finnish (NFE) AF: 0.000207 AC: 230 AN: 1111952

Other (OTH) AF: 0.0104 AC: 627 AN: 60388

GnomAD4 genome AF: 0.0496 AC: 7550 AN: 152250 Hom.: 669 Cov.: 32 AF XY: 0.0489 AC XY: 3636 AN XY: 74428

African (AFR) AF: 0.173 AC: 7189 AN: 41514

American (AMR) AF: 0.0165 AC: 253 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68020

Other (OTH) AF: 0.0355 AC: 75 AN: 2114

Alfa AF: 0.0203 Hom.: 150

Bravo AF: 0.0558

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000296

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		0.20
Mutation Taster		=91/9	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10115304; hg19: chr9-129458628;