12-71524407-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003667.4(LGR5):c.286C>T(p.Arg96Cys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000186 in 1,610,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003667.4 missense, splice_region
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 |
---|---|---|---|---|---|---|---|---|
LGR5 | NM_003667.4 | c.286C>T | p.Arg96Cys | missense_variant, splice_region_variant | Exon 3 of 18 | ENST00000266674.10 | NP_003658.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LGR5 | ENST00000266674.10 | c.286C>T | p.Arg96Cys | missense_variant, splice_region_variant | Exon 3 of 18 | 1 | NM_003667.4 | ENSP00000266674.4 | ||
LGR5 | ENST00000540815.2 | c.286C>T | p.Arg96Cys | missense_variant, splice_region_variant | Exon 3 of 17 | 1 | ENSP00000441035.2 | |||
LGR5 | ENST00000536515.5 | c.286C>T | p.Arg96Cys | missense_variant, splice_region_variant | Exon 3 of 17 | 1 | ENSP00000443033.1 | |||
LGR5 | ENST00000550851.5 | n.383C>T | splice_region_variant, non_coding_transcript_exon_variant | Exon 3 of 20 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250184Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135300
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1458564Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 725834
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74350
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.286C>T (p.R96C) alteration is located in exon 3 (coding exon 3) of the LGR5 gene. This alteration results from a C to T substitution at nucleotide position 286, causing the arginine (R) at amino acid position 96 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at