Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP2BP4_ModerateBP6_ModerateBS2

The NM_001174147.2(LMX1B):c.1107C>A(p.Ser369Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000088 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. S369S) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

LMX1B
NM_001174147.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.195

Publications

3 publications found

Variant links:

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

LMX1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 33 curated pathogenic missense variants (we use a threshold of 10). The gene has 8 curated benign missense variants. Gene score misZ: 2.0208 (below the threshold of 3.09). Trascript score misZ: 1.8847 (below the threshold of 3.09). GenCC associations: The gene is linked to nail-patella-like renal disease, nail-patella syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.068713635).

BP6

Variant 9-126696349-C-A is Benign according to our data. Variant chr9-126696349-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2754215.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 26 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LMX1B	NM_001174147.2	MANE Select	c.1107C>A	p.Ser369Arg	missense	Exon 8 of 8	NP_001167618.1
LMX1B	NM_001174146.2		c.1119C>A	p.Ser373Arg	missense	Exon 8 of 8	NP_001167617.1
LMX1B	NM_002316.4		c.1086C>A	p.Ser362Arg	missense	Exon 8 of 8	NP_002307.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LMX1B	ENST00000373474.9	TSL:1 MANE Select	c.1107C>A	p.Ser369Arg	missense	Exon 8 of 8	ENSP00000362573.3
LMX1B	ENST00000355497.10	TSL:1	c.1119C>A	p.Ser373Arg	missense	Exon 8 of 8	ENSP00000347684.5
LMX1B	ENST00000526117.6	TSL:1	c.1086C>A	p.Ser362Arg	missense	Exon 8 of 8	ENSP00000436930.1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000199

AC:

AN:

251328

AF XY:

0.000191

show subpopulations

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:

0.00217

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000794

AC:

116

AN:

1461780

Hom.:

Cov.:

AF XY:

0.0000715

AC XY:

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00208

AC:

111

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111952

Other (OTH)

AF:

0.0000497

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000171

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41412

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00245

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

150

ExAC

AF:

0.000173

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.56

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.069

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.1

PhyloP100

0.20

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.45

Sift

Benign

0.16

Sift4G

Benign

0.47

Polyphen

0.013

Vest4

0.76

MVP

0.97

MPC

0.90

ClinPred

0.093

GERP RS

2.4

Varity_R

0.23

gMVP

0.79

Mutation Taster

=4/96

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_001174147.2:c.1107C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over