11-6390605-C-CGCTTTGTGAT
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000543.5(SMPD1):c.10_11insTTGTGATGCT(p.Tyr4PhefsTer51) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,032 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R3R) has been classified as Likely benign.
Frequency
Consequence
NM_000543.5 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.10_11insTTGTGATGCT | p.Tyr4PhefsTer51 | frameshift_variant | 1/6 | ENST00000342245.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMPD1 | ENST00000342245.9 | c.10_11insTTGTGATGCT | p.Tyr4PhefsTer51 | frameshift_variant | 1/6 | 1 | NM_000543.5 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460032Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726368
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Niemann-Pick disease, type A Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | May 11, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.