rs763392279
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006459.4(ERLIN1):c.773C>T(p.Ala258Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,613,694 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A258A) has been classified as Likely benign.
Frequency
Consequence
NM_006459.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERLIN1 | NM_006459.4 | c.773C>T | p.Ala258Val | missense_variant | 10/11 | ENST00000421367.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERLIN1 | ENST00000421367.7 | c.773C>T | p.Ala258Val | missense_variant | 10/11 | 1 | NM_006459.4 | P1 | |
ERLIN1 | ENST00000407654.7 | c.773C>T | p.Ala258Val | missense_variant | 11/12 | 1 | P1 | ||
ERLIN1 | ENST00000370408.2 | c.773C>T | p.Ala258Val | missense_variant | 11/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251096Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135694
GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461570Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18AN XY: 727060
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74314
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 08, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Hereditary spastic paraplegia 62 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 15, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 258 of the ERLIN1 protein (p.Ala258Val). This variant is present in population databases (rs763392279, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ERLIN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 476196). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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