rs587776711
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1PP5
The NM_178138.6(LHX3):c.452_454+20del variant causes a splice donor, splice donor 5th base, coding sequence, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. R151R) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 34)
Consequence
LHX3
NM_178138.6 splice_donor, splice_donor_5th_base, coding_sequence, intron
NM_178138.6 splice_donor, splice_donor_5th_base, coding_sequence, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.472
Genes affected
LHX3 (HGNC:6595): (LIM homeobox 3) This gene encodes a member of a large family of proteins which carry the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor that is required for pituitary development and motor neuron specification. Mutations in this gene cause combined pituitary hormone deficiency 3. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Splicing variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PP5
?
Variant 9-136199657-AGCGTCGTCCCCTCGGCTGACCTC-A is Pathogenic according to our data. Variant chr9-136199657-AGCGTCGTCCCCTCGGCTGACCTC-A is described in ClinVar as [Pathogenic]. Clinvar id is 9022.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-136199657-AGCGTCGTCCCCTCGGCTGACCTC-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LHX3 | NM_178138.6 | c.452_454+20del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 3/6 | ENST00000371748.10 | ||
LHX3 | NM_001363746.1 | c.419_421+20del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 3/6 | |||
LHX3 | NM_014564.5 | c.467_469+20del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 3/6 | |||
LHX3 | XM_017015168.1 | c.380_382+20del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LHX3 | ENST00000371748.10 | c.452_454+20del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 3/6 | 1 | NM_178138.6 | |||
LHX3 | ENST00000371746.9 | c.467_469+20del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 3/6 | 1 | P1 | |||
LHX3 | ENST00000619587.1 | c.419_421+20del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 3/6 | 1 | ||||
LHX3 | ENST00000645419.1 | n.1277_1279+20del | splice_donor_variant, splice_donor_5th_base_variant, non_coding_transcript_exon_variant, intron_variant | 2/5 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Non-acquired combined pituitary hormone deficiency with spine abnormalities Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 15, 2008 | - - |
Pathogenic, no assertion criteria provided | curation | Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University | Dec 30, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at