rs1553774967
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001122752.2(SERPINI1):c.843C>G(p.Asn281Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001122752.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SERPINI1 | NM_001122752.2 | c.843C>G | p.Asn281Lys | missense_variant | Exon 5 of 9 | ENST00000446050.7 | NP_001116224.1 | |
SERPINI1 | NM_005025.5 | c.843C>G | p.Asn281Lys | missense_variant | Exon 5 of 9 | NP_005016.1 | ||
SERPINI1 | XM_017006618.3 | c.843C>G | p.Asn281Lys | missense_variant | Exon 5 of 9 | XP_016862107.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SERPINI1 | ENST00000446050.7 | c.843C>G | p.Asn281Lys | missense_variant | Exon 5 of 9 | 1 | NM_001122752.2 | ENSP00000397373.2 | ||
SERPINI1 | ENST00000295777.9 | c.843C>G | p.Asn281Lys | missense_variant | Exon 5 of 9 | 1 | ENSP00000295777.5 | |||
SERPINI1 | ENST00000472747.2 | c.*107C>G | downstream_gene_variant | 3 | ENSP00000420561.2 | |||||
ENSG00000287319 | ENST00000661269.1 | n.*161G>C | downstream_gene_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Familial encephalopathy with neuroserpin inclusion bodies Uncertain:1
This sequence change replaces asparagine with lysine at codon 281 of the SERPINI1 protein (p.Asn281Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SERPINI1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). In summary, this variant is a novel missense change with uncertain impact on protein function. 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