rs149682257
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_080424.4(SP110):c.1612G>A(p.Glu538Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000501 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_080424.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SP110 | NM_080424.4 | c.1612G>A | p.Glu538Lys | missense_variant | 15/19 | ENST00000258381.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SP110 | ENST00000258381.11 | c.1612G>A | p.Glu538Lys | missense_variant | 15/19 | 2 | NM_080424.4 | P1 | |
ENST00000628587.2 | n.1098+745C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.000315 AC: 48AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000247 AC: 62AN: 251416Hom.: 0 AF XY: 0.000265 AC XY: 36AN XY: 135886
GnomAD4 exome AF: 0.000521 AC: 761AN: 1461632Hom.: 0 Cov.: 31 AF XY: 0.000483 AC XY: 351AN XY: 727124
GnomAD4 genome AF: 0.000315 AC: 48AN: 152306Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19AN XY: 74480
ClinVar
Submissions by phenotype
Hepatic veno-occlusive disease-immunodeficiency syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 538 of the SP110 protein (p.Glu538Lys). This variant is present in population databases (rs149682257, gnomAD 0.05%). 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: 579573). 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 lysine 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. - |
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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at