rs756746930
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_080424.4(SP110):c.86A>T(p.Lys29Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K29N) has been classified as Uncertain significance.
Frequency
Consequence
NM_080424.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SP110 | NM_080424.4 | c.86A>T | p.Lys29Met | missense_variant | 2/19 | ENST00000258381.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SP110 | ENST00000258381.11 | c.86A>T | p.Lys29Met | missense_variant | 2/19 | 2 | NM_080424.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251190Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135732
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461822Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727222
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Hepatic veno-occlusive disease-immunodeficiency syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change replaces lysine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 29 of the SP110 protein (p.Lys29Met). This variant is present in population databases (rs756746930, gnomAD 0.03%). 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: 577020). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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