11-72080886-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_145309.6(LRRC51):c.-140+1G>T variant causes a splice donor, intron change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_145309.6 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRRC51 | NM_145309.6 | c.-140+1G>T | splice_donor_variant, intron_variant | Intron 1 of 5 | ENST00000289488.8 | NP_660352.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRRC51 | ENST00000289488.8 | c.-140+1G>T | splice_donor_variant, intron_variant | Intron 1 of 5 | 1 | NM_145309.6 | ENSP00000289488.2 | |||
LRTOMT | ENST00000307198.11 | c.-322+1G>T | splice_donor_variant, intron_variant | Intron 1 of 6 | 2 | ENSP00000305742.7 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 314Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 220
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 63 Uncertain:1
This variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. It was observed by ICSL 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 for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene and cDNA change. No publications were found based on this search. Due to the potential impact of splice donor variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at