chr3-155828218-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004733.4(SLC33A1):c.1642A>G(p.Asn548Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,611,864 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC33A1 | NM_004733.4 | c.1642A>G | p.Asn548Asp | missense_variant | 6/6 | ENST00000643144.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC33A1 | ENST00000643144.2 | c.1642A>G | p.Asn548Asp | missense_variant | 6/6 | NM_004733.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000123 AC: 31AN: 251394Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135886
GnomAD4 exome AF: 0.000117 AC: 171AN: 1459672Hom.: 1 Cov.: 29 AF XY: 0.000124 AC XY: 90AN XY: 726352
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 27, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 11, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 29, 2022 | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 548 of the SLC33A1 protein (p.Asn548Asp). This variant is present in population databases (rs767949889, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SLC33A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 959598). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at