rs3838786
Positions:
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-T
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-TGCTGGC
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-TGCTGGCGCTGGC
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-TGCTGGCGCTGGCGCTGGC
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-TGCTGGCGCTGGCGCTGGCGCTGGCGCTGGC
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-TGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGC
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-TGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGC
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-TGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGC
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000543.5(SMPD1):βc.120_143delβ(p.Ala42_Leu49del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000326 in 1,594,986 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ).
Frequency
Genomes: π 0.000048 ( 0 hom., cov: 0)
Exomes π: 0.000031 ( 0 hom. )
Consequence
SMPD1
NM_000543.5 inframe_deletion
NM_000543.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.65
Genes affected
SMPD1 (HGNC:11120): (sphingomyelin phosphodiesterase 1) The protein encoded by this gene is a lysosomal acid sphingomyelinase that converts sphingomyelin to ceramide. The encoded protein also has phospholipase C activity. Defects in this gene are a cause of Niemann-Pick disease type A (NPA) and Niemann-Pick disease type B (NPB). Multiple transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMPD1 | NM_000543.5 | c.120_143del | p.Ala42_Leu49del | inframe_deletion | 1/6 | ENST00000342245.9 | NP_000534.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMPD1 | ENST00000342245.9 | c.120_143del | p.Ala42_Leu49del | inframe_deletion | 1/6 | 1 | NM_000543.5 | ENSP00000340409 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000475 AC: 7AN: 147228Hom.: 0 Cov.: 0
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GnomAD4 exome AF: 0.0000311 AC: 45AN: 1447758Hom.: 0 AF XY: 0.0000347 AC XY: 25AN XY: 720014
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GnomAD4 genome AF: 0.0000475 AC: 7AN: 147228Hom.: 0 Cov.: 0 AF XY: 0.0000278 AC XY: 2AN XY: 71866
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Niemann-Pick disease, type A;C0268243:Niemann-Pick disease, type B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 01, 2021 | This variant, c.120_143del, results in the deletion of 8 amino acid(s) of the SMPD1 protein (p.Ala42_Leu49del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SMPD1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at