11-6390640-GT-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000543.5(SMPD1):c.43del(p.Ser15ProfsTer62) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,934 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. S15S) has been classified as Likely benign.
Frequency
Consequence
NM_000543.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMPD1 | NM_000543.5 | c.43del | p.Ser15ProfsTer62 | frameshift_variant | 1/6 | ENST00000342245.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMPD1 | ENST00000342245.9 | c.43del | p.Ser15ProfsTer62 | frameshift_variant | 1/6 | 1 | NM_000543.5 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1460934Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726830
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Niemann-Pick disease, type A;C0268243:Niemann-Pick disease, type B Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 09, 2022 | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SMPD1-related conditions. This sequence change creates a premature translational stop signal (p.Ser15Profs*62) in the SMPD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMPD1 are known to be pathogenic (PMID: 12369017, 15221801). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.