rs775568984
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_000543.5(SMPD1):c.108_109insGCG(p.Val36_Leu37insAla) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V36V) has been classified as Benign.
Frequency
Genomes: 𝑓 0.0053 ( 5 hom., cov: 0)
Exomes 𝑓: 0.0048 ( 106 hom. )
Failed GnomAD Quality Control
Consequence
SMPD1
NM_000543.5 inframe_insertion
NM_000543.5 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.158
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 Benign. Variant got -16 ACMG points.
BP6
?
Variant 11-6390705-T-TGGC is Benign according to our data. Variant chr11-6390705-T-TGGC is described in ClinVar as [Likely_benign]. Clinvar id is 529235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00526 (775/147350) while in subpopulation SAS AF= 0.0345 (160/4642). AF 95% confidence interval is 0.0301. There are 5 homozygotes in gnomad4. There are 455 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMPD1 | NM_000543.5 | c.108_109insGCG | p.Val36_Leu37insAla | inframe_insertion | 1/6 | ENST00000342245.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMPD1 | ENST00000342245.9 | c.108_109insGCG | p.Val36_Leu37insAla | inframe_insertion | 1/6 | 1 | NM_000543.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00528 AC: 777AN: 147224Hom.: 6 Cov.: 0
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GnomAD3 exomes AF: 0.00721 AC: 1724AN: 238972Hom.: 37 AF XY: 0.00793 AC XY: 1036AN XY: 130606
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00478 AC: 6924AN: 1447752Hom.: 106 Cov.: 0 AF XY: 0.00546 AC XY: 3931AN XY: 720008
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome ? AF: 0.00526 AC: 775AN: 147350Hom.: 5 Cov.: 0 AF XY: 0.00632 AC XY: 455AN XY: 71996
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital | Feb 02, 2020 | - - |
Niemann-Pick disease, type A;C0268243:Niemann-Pick disease, type B Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 11, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 13, 2020 | See Variant Classification Assertion Criteria. - |
Niemann-Pick disease, type A Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 25, 2017 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at