rs199915216
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_000543.5(SMPD1):c.1598C>A(p.Pro533Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P533L) has been classified as Likely benign.
Frequency
Consequence
NM_000543.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMPD1 | NM_000543.5 | c.1598C>A | p.Pro533Gln | missense_variant | 6/6 | ENST00000342245.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMPD1 | ENST00000342245.9 | c.1598C>A | p.Pro533Gln | missense_variant | 6/6 | 1 | NM_000543.5 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251296Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135788
GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461866Hom.: 0 Cov.: 34 AF XY: 0.0000468 AC XY: 34AN XY: 727232
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74376
ClinVar
Submissions by phenotype
Niemann-Pick disease, type A Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 28, 2024 | - - |
Pathogenic, criteria provided, single submitter | research | Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS | Apr 25, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at