rs145145840
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_000271.5(NPC1):c.3198C>T(p.Thr1066Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,614,144 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000271.5 synonymous
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NPC1 | NM_000271.5 | c.3198C>T | p.Thr1066Thr | synonymous_variant | Exon 21 of 25 | ENST00000269228.10 | NP_000262.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NPC1 | ENST00000269228.10 | c.3198C>T | p.Thr1066Thr | synonymous_variant | Exon 21 of 25 | 1 | NM_000271.5 | ENSP00000269228.4 | ||
NPC1 | ENST00000591051.1 | c.2274C>T | p.Thr758Thr | synonymous_variant | Exon 14 of 18 | 2 | ENSP00000467636.1 | |||
NPC1 | ENST00000591955.1 | n.541C>T | non_coding_transcript_exon_variant | Exon 2 of 2 | 4 | |||||
NPC1 | ENST00000591075.1 | n.*22C>T | downstream_gene_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.000986 AC: 150AN: 152166Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00104 AC: 262AN: 251408Hom.: 1 AF XY: 0.00110 AC XY: 149AN XY: 135888
GnomAD4 exome AF: 0.00116 AC: 1699AN: 1461860Hom.: 4 Cov.: 32 AF XY: 0.00117 AC XY: 854AN XY: 727232
GnomAD4 genome AF: 0.000985 AC: 150AN: 152284Hom.: 1 Cov.: 32 AF XY: 0.00111 AC XY: 83AN XY: 74456
ClinVar
Submissions by phenotype
Niemann-Pick disease, type C1 Uncertain:1Benign:5
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
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not provided Uncertain:1Benign:2
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NPC1: BP4, BP7 -
not specified Benign:1
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Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at