NM_177398.4:c.263+12127G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_177398.4(LMX1A):​c.263+12127G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 152,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 30)

Consequence

LMX1A
NM_177398.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.215

Publications

1 publications found
Variant links:
Genes affected
LMX1A (HGNC:6653): (LIM homeobox transcription factor 1 alpha) This gene encodes a homeodomain and LIM-domain containing protein. The encoded protein is a transcription factor that acts as a positive regulator of insulin gene transcription. This gene also plays a role in the development of dopamine producing neurons during embryogenesis. Mutations in this gene are associated with an increased risk of developing Parkinson's disease. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]
LMX1A Gene-Disease associations (from GenCC):
  • autosomal dominant nonsyndromic hearing loss 7
    Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
  • Mobius syndrome
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
  • hearing loss, autosomal recessive
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LMX1ANM_177398.4 linkc.263+12127G>T intron_variant Intron 3 of 8 ENST00000342310.7 NP_796372.1 Q8TE12-1
LMX1ANM_001174069.2 linkc.263+12127G>T intron_variant Intron 3 of 8 NP_001167540.1 Q8TE12-1
LMX1AXM_011509540.3 linkc.263+12127G>T intron_variant Intron 3 of 7 XP_011507842.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LMX1AENST00000342310.7 linkc.263+12127G>T intron_variant Intron 3 of 8 2 NM_177398.4 ENSP00000340226.3 Q8TE12-1
LMX1AENST00000367893.4 linkc.263+12127G>T intron_variant Intron 2 of 7 1 ENSP00000356868.4 Q8TE12-1
LMX1AENST00000294816.6 linkc.263+12127G>T intron_variant Intron 3 of 8 2 ENSP00000294816.2 Q8TE12-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152068
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152068
Hom.:
0
Cov.:
30
AF XY:
0.0000269
AC XY:
2
AN XY:
74274
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41370
American (AMR)
AF:
0.000131
AC:
2
AN:
15268
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5188
South Asian (SAS)
AF:
0.000208
AC:
1
AN:
4816
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10602
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68038
Other (OTH)
AF:
0.00
AC:
0
AN:
2086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.545
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
2978

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
1.6
DANN
Benign
0.12
PhyloP100
0.21

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: rs6702087; hg19: chr1-165310186; API