chr18-23541154-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_000271.5(NPC1):c.2428G>A(p.Val810Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,614,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V810F) has been classified as Likely benign.
Frequency
Consequence
NM_000271.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPC1 | NM_000271.5 | c.2428G>A | p.Val810Ile | missense_variant | 16/25 | ENST00000269228.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPC1 | ENST00000269228.10 | c.2428G>A | p.Val810Ile | missense_variant | 16/25 | 1 | NM_000271.5 | P1 | |
NPC1 | ENST00000591051.1 | c.1507G>A | p.Val503Ile | missense_variant | 9/18 | 2 | |||
NPC1 | ENST00000540608.5 | n.2342G>A | non_coding_transcript_exon_variant | 14/16 | 2 | ||||
NPC1 | ENST00000586718.1 | n.219G>A | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000227 AC: 57AN: 251482Hom.: 0 AF XY: 0.000316 AC XY: 43AN XY: 135912
GnomAD4 exome AF: 0.000142 AC: 207AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 147AN XY: 727242
GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74480
ClinVar
Submissions by phenotype
NPC1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 20, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Niemann-Pick disease, type C1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at