rs200885656
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_004733.4(SLC33A1):āc.288A>Cā(p.Pro96=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,614,052 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00035 ( 0 hom., cov: 32)
Exomes š: 0.00025 ( 1 hom. )
Consequence
SLC33A1
NM_004733.4 synonymous
NM_004733.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.07
Genes affected
SLC33A1 (HGNC:95): (solute carrier family 33 member 1) The protein encoded by this gene is required for the formation of O-acetylated (Ac) gangliosides. The encoded protein is predicted to contain 6 to 10 transmembrane domains, and a leucine zipper motif in transmembrane domain III. Defects in this gene have been reported to cause spastic paraplegia autosomal dominant type 42 (SPG42) in one Chinese family, but not in similar patients of European descent. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 3-155853710-T-G is Benign according to our data. Variant chr3-155853710-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 586608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-155853710-T-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-3.07 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC33A1 | NM_004733.4 | c.288A>C | p.Pro96= | synonymous_variant | 1/6 | ENST00000643144.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC33A1 | ENST00000643144.2 | c.288A>C | p.Pro96= | synonymous_variant | 1/6 | NM_004733.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000348 AC: 53AN: 152090Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00112 AC: 282AN: 251380Hom.: 1 AF XY: 0.000824 AC XY: 112AN XY: 135912
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GnomAD4 exome AF: 0.000250 AC: 365AN: 1461844Hom.: 1 Cov.: 32 AF XY: 0.000210 AC XY: 153AN XY: 727224
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GnomAD4 genome ? AF: 0.000355 AC: 54AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24AN XY: 74416
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 15, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 22, 2021 | - - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at