rs775860642
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_000543.5(SMPD1):c.107_112del(p.Val36_Leu37del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,546,720 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L35L) has been classified as Likely benign.
Frequency
Consequence
NM_000543.5 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMPD1 | NM_000543.5 | c.107_112del | p.Val36_Leu37del | inframe_deletion | 1/6 | ENST00000342245.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMPD1 | ENST00000342245.9 | c.107_112del | p.Val36_Leu37del | inframe_deletion | 1/6 | 1 | NM_000543.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00141 AC: 196AN: 139132Hom.: 0 Cov.: 0
GnomAD3 exomes AF: 0.00264 AC: 613AN: 232506Hom.: 17 AF XY: 0.00269 AC XY: 342AN XY: 126968
GnomAD4 exome AF: 0.00183 AC: 2572AN: 1407484Hom.: 16 AF XY: 0.00188 AC XY: 1318AN XY: 700306
GnomAD4 genome ? AF: 0.00141 AC: 196AN: 139236Hom.: 0 Cov.: 0 AF XY: 0.00165 AC XY: 112AN XY: 67720
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | SMPD1: PM4, BS2 - |
Sphingomyelin/cholesterol lipidosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 08, 2022 | Variant summary: SMPD1 c.107_112delTGCTGG (p.Val36_Leu37del) results in an in-frame deletion that is predicted to remove two amino acids from the encoded protein. The variant allele was found at a frequency of 0.0026 in 232506 control chromosomes, predominantly at a frequency of 0.0038 within the South Asian subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 1.7 fold of the estimated maximal expected allele frequency for a pathogenic variant in SMPD1 causing Niemann-Pick Disease phenotype (0.0022), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Two classified as benign/likely benign while one classified as VUS. Based on the evidence outlined above, the variant was classified as benign. - |
SMPD1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 15, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Niemann-Pick disease, type A;C0268243:Niemann-Pick disease, type B Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Niemann-Pick disease, type A Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 10, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at