chr3-155828301-A-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004733.4(SLC33A1):āc.1559T>Cā(p.Ile520Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000155 in 1,606,000 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I520S) has been classified as Uncertain significance.
Frequency
Consequence
NM_004733.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC33A1 | NM_004733.4 | c.1559T>C | p.Ile520Thr | missense_variant | 6/6 | ENST00000643144.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC33A1 | ENST00000643144.2 | c.1559T>C | p.Ile520Thr | missense_variant | 6/6 | NM_004733.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000255 AC: 64AN: 251318Hom.: 0 AF XY: 0.000272 AC XY: 37AN XY: 135848
GnomAD4 exome AF: 0.000159 AC: 231AN: 1453740Hom.: 2 Cov.: 27 AF XY: 0.000202 AC XY: 146AN XY: 723824
GnomAD4 genome AF: 0.000118 AC: 18AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74462
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 42 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 12, 2024 | - - |
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLC33A1 protein function. ClinVar contains an entry for this variant (Variation ID: 1043753). This variant has not been reported in the literature in individuals affected with SLC33A1-related conditions. This variant is present in population databases (rs777143987, gnomAD 0.2%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 520 of the SLC33A1 protein (p.Ile520Thr). - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Sep 23, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at