18-23544958-A-G
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_000271.5(NPC1):c.1947+2T>C variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000247 in 1,216,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Consequence
NM_000271.5 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NPC1 | NM_000271.5 | c.1947+2T>C | splice_donor_variant, intron_variant | Intron 12 of 24 | ENST00000269228.10 | NP_000262.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NPC1 | ENST00000269228.10 | c.1947+2T>C | splice_donor_variant, intron_variant | Intron 12 of 24 | 1 | NM_000271.5 | ENSP00000269228.4 | |||
NPC1 | ENST00000591051.1 | c.1023+2T>C | splice_donor_variant, intron_variant | Intron 5 of 17 | 2 | ENSP00000467636.1 | ||||
NPC1 | ENST00000540608.5 | n.1861+2T>C | splice_donor_variant, intron_variant | Intron 10 of 15 | 2 |
Frequencies
GnomAD3 genomes Cov.: 16
GnomAD4 exome AF: 0.00000247 AC: 3AN: 1216764Hom.: 0 Cov.: 27 AF XY: 0.00000325 AC XY: 2AN XY: 614894
GnomAD4 genome Cov.: 16
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at