rs181058279
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_080424.4(SP110):āc.2122G>Cā(p.Gly708Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000892 in 1,612,512 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. G708S) has been classified as Uncertain significance.
Frequency
Consequence
NM_080424.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SP110 | NM_080424.4 | c.2122G>C | p.Gly708Arg | missense_variant | 19/19 | ENST00000258381.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SP110 | ENST00000258381.11 | c.2122G>C | p.Gly708Arg | missense_variant | 19/19 | 2 | NM_080424.4 | P1 | |
ENST00000628587.2 | n.1003+1492C>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000494 AC: 75AN: 151956Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000378 AC: 95AN: 251420Hom.: 0 AF XY: 0.000390 AC XY: 53AN XY: 135874
GnomAD4 exome AF: 0.000933 AC: 1363AN: 1460438Hom.: 3 Cov.: 29 AF XY: 0.000877 AC XY: 637AN XY: 726616
GnomAD4 genome ? AF: 0.000493 AC: 75AN: 152074Hom.: 0 Cov.: 31 AF XY: 0.000404 AC XY: 30AN XY: 74344
ClinVar
Submissions by phenotype
Hepatic veno-occlusive disease-immunodeficiency syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 684 of the SP110 protein (p.Gly684Arg). This variant is present in population databases (rs181058279, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with SP110-related conditions. ClinVar contains an entry for this variant (Variation ID: 577709). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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