rs529668402

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 8P and 9B. PVS1BP6BS1BS2

The NM_001174146.2(LMX1B):c.904C>T(p.Gln302*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 1,173,816 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00096 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

LMX1B
NM_001174146.2 stop_gained

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: 0.237

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

BP6

Variant 9-126693830-C-T is Benign according to our data. Variant chr9-126693830-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 258630.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=2}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00096 (146/152066) while in subpopulation AFR AF= 0.00338 (140/41456). AF 95% confidence interval is 0.00292. There are 1 homozygotes in gnomad4. There are 79 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 146 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2 link	c.886+18C>T		intron_variant	Intron 6 of 7	ENST00000373474.9	NP_001167618.1	O60663-1Q6ISE0
LMX1B	NM_001174146.2 link	c.904C>T	p.Gln302*	stop_gained	Exon 6 of 8		NP_001167617.1	B7ZLH2
LMX1B	NM_002316.4 link	c.886+18C>T		intron_variant	Intron 6 of 7		NP_002307.2	O60663-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LMX1B	ENST00000355497.10 link	c.904C>T	p.Gln302*	stop_gained	Exon 6 of 8	1		ENSP00000347684.5	O60663-3
LMX1B	ENST00000373474.9 link	c.886+18C>T		intron_variant	Intron 6 of 7	1	NM_001174147.2	ENSP00000362573.3	O60663-1
LMX1B	ENST00000526117.6 link	c.886+18C>T		intron_variant	Intron 6 of 7	1		ENSP00000436930.1	O60663-2

Frequencies

GnomAD3 genomes

AF:

0.000961

AC:

146

AN:

151948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000108

AC:

AN:

130230

Hom.:

AF XY:

0.0000561

AC XY:

AN XY:

71254

show subpopulations

Gnomad AFR exome

AF:

0.00206

Gnomad AMR exome

AF:

0.0000410

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000910

AC:

AN:

1021750

Hom.:

Cov.:

AF XY:

0.0000675

AC XY:

AN XY:

518390

show subpopulations

Gnomad4 AFR exome

AF:

0.00329

Gnomad4 AMR exome

AF:

0.0000569

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000218

GnomAD4 genome

AF:

0.000960

AC:

146

AN:

152066

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00338

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000712

Hom.:

Bravo

AF:

0.00111

ExAC

AF:

0.0000588

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

LMX1B-related disorder

Uncertain:1

Jan 01, 2024

Daryl Scott Lab, Baylor College of Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BS1, BS2 -

Nail-patella syndrome

Uncertain:1

Nov 11, 2020

Daryl Scott Lab, Baylor College of Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Dec 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Pathogenic

0.27

CADD

Benign

6.7

DANN

Benign

0.96

Eigen

Benign

-0.051

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.0087

Vest4

0.23

GERP RS

-0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over