9-126690941-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001174147.2(LMX1B):​c.432C>T​(p.Cys144Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,614,056 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000075 ( 1 hom. )

Consequence

LMX1B
NM_001174147.2 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0580

Publications

0 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
Variant 9-126690941-C-T is Benign according to our data. Variant chr9-126690941-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.058 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000591 (9/152312) while in subpopulation SAS AF = 0.00166 (8/4826). AF 95% confidence interval is 0.000824. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
BS2
High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LMX1BNM_001174147.2 linkc.432C>T p.Cys144Cys synonymous_variant Exon 3 of 8 ENST00000373474.9 NP_001167618.1 O60663-1Q6ISE0
LMX1BNM_001174146.2 linkc.432C>T p.Cys144Cys synonymous_variant Exon 3 of 8 NP_001167617.1 B7ZLH2
LMX1BNM_002316.4 linkc.432C>T p.Cys144Cys synonymous_variant Exon 3 of 8 NP_002307.2 O60663-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LMX1BENST00000373474.9 linkc.432C>T p.Cys144Cys synonymous_variant Exon 3 of 8 1 NM_001174147.2 ENSP00000362573.3 O60663-1
LMX1BENST00000355497.10 linkc.432C>T p.Cys144Cys synonymous_variant Exon 3 of 8 1 ENSP00000347684.5 O60663-3
LMX1BENST00000526117.6 linkc.432C>T p.Cys144Cys synonymous_variant Exon 3 of 8 1 ENSP00000436930.1 O60663-2

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152194
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00166
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000163
AC:
41
AN:
250840
AF XY:
0.000177
show subpopulations
Gnomad AFR exome
AF:
0.0000618
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000746
AC:
109
AN:
1461744
Hom.:
1
Cov.:
31
AF XY:
0.000103
AC XY:
75
AN XY:
727184
show subpopulations
African (AFR)
AF:
0.000119
AC:
4
AN:
33478
American (AMR)
AF:
0.00
AC:
0
AN:
44714
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26124
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39694
South Asian (SAS)
AF:
0.00103
AC:
89
AN:
86252
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53394
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000899
AC:
10
AN:
1111932
Other (OTH)
AF:
0.0000828
AC:
5
AN:
60388
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.496
Heterozygous variant carriers
0
8
16
23
31
39
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4
8
12
16
20
<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:
0.0000591
AC:
9
AN:
152312
Hom.:
0
Cov.:
34
AF XY:
0.0000537
AC XY:
4
AN XY:
74470
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41576
American (AMR)
AF:
0.00
AC:
0
AN:
15310
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5174
South Asian (SAS)
AF:
0.00166
AC:
8
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68016
Other (OTH)
AF:
0.00
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.447
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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.:
0
Bravo
AF:
0.0000378
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
Jul 30, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Nail-patella syndrome;C0403548:Nail-patella-like renal disease Benign:1
Jul 06, 2021
Fulgent Genetics, Fulgent Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Focal segmental glomerulosclerosis Benign:1
May 14, 2021
Genome Diagnostics Laboratory, The Hospital for Sick Children
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Nail-patella syndrome Benign:1
Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
CADD
Benign
13
DANN
Benign
0.95
PhyloP100
-0.058
Mutation Taster
=89/11
polymorphism

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

Other links and lift over

dbSNP: rs375657880; hg19: chr9-129453220; API