rs141659629
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_000271.5(NPC1):c.3558C>T(p.Arg1186=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R1186R) has been classified as Likely benign.
Frequency
Consequence
NM_000271.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPC1 | NM_000271.5 | c.3558C>T | p.Arg1186= | synonymous_variant | 23/25 | ENST00000269228.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPC1 | ENST00000269228.10 | c.3558C>T | p.Arg1186= | synonymous_variant | 23/25 | 1 | NM_000271.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152258Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000518 AC: 13AN: 251086Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135728
GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461584Hom.: 0 Cov.: 30 AF XY: 0.0000275 AC XY: 20AN XY: 727100
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152258Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74386
ClinVar
Submissions by phenotype
Niemann-Pick disease, type C1 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 22, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at