chr1-180230530-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_SupportingPM2
The NM_033343.4(LHX4):āc.1A>Gā(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00000657 in 152,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Consequence
NM_033343.4 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LHX4 | NM_033343.4 | c.1A>G | p.Met1? | start_lost | Exon 1 of 6 | ENST00000263726.4 | NP_203129.1 | |
LHX4 | XM_011510105.3 | c.-108+1617A>G | intron_variant | Intron 1 of 5 | XP_011508407.1 | |||
LHX4 | XM_011510106.4 | c.-108+1377A>G | intron_variant | Intron 1 of 5 | XP_011508408.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 31
GnomAD4 exome Cov.: 30
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74332
ClinVar
Submissions by phenotype
LHX4-related disorder Uncertain:1
The LHX4 c.1A>G variant is predicted to disrupt the translation initiation site (Start loss). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. This variant impacts a highly conserved base as well as a highly conserved residue in the LHX4 gene. However, the impacted residue is adjacent to another Methionine codon, which may be used as the translation start site in the presence of this variant. Start-loss variants are frequently pathogenic. However, although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at