rs750345585
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000543.5(SMPD1):c.1166G>A(p.Arg389His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,786 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R389C) has been classified as Uncertain significance.
Frequency
Consequence
NM_000543.5 missense
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMPD1 | NM_000543.5 | c.1166G>A | p.Arg389His | missense_variant | 3/6 | ENST00000342245.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMPD1 | ENST00000342245.9 | c.1166G>A | p.Arg389His | missense_variant | 3/6 | 1 | NM_000543.5 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152122Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249312Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135250
GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461664Hom.: 0 Cov.: 31 AF XY: 0.0000371 AC XY: 27AN XY: 727122
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152122Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74306
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 26, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 16, 2019 | - - |
Niemann-Pick disease, type A;C0268243:Niemann-Pick disease, type B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2021 | This sequence change replaces arginine with histidine at codon 389 of the SMPD1 protein (p.Arg389His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs750345585, ExAC 0.005%). This missense change has been observed in individual(s) with Niemann-Pick disease (PMID: 28302345). ClinVar contains an entry for this variant (Variation ID: 557533). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Niemann-Pick disease, type A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Mar 28, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at