rs756818970
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001122752.2(SERPINI1):āc.914A>Cā(p.Asp305Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D305V) has been classified 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINI1 | NM_001122752.2 | c.914A>C | p.Asp305Ala | missense_variant | 6/9 | ENST00000446050.7 | |
SERPINI1 | NM_005025.5 | c.914A>C | p.Asp305Ala | missense_variant | 6/9 | ||
SERPINI1 | XM_017006618.3 | c.914A>C | p.Asp305Ala | missense_variant | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINI1 | ENST00000446050.7 | c.914A>C | p.Asp305Ala | missense_variant | 6/9 | 1 | NM_001122752.2 | P1 | |
ENST00000661269.1 | n.545+3261T>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460568Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 726660
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Familial encephalopathy with neuroserpin inclusion bodies Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 305 of the SERPINI1 protein (p.Asp305Ala). This variant is not present in population databases (gnomAD no frequency). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SERPINI1 protein function. ClinVar contains an entry for this variant (Variation ID: 534957). This variant has not been reported in the literature in individuals affected with SERPINI1-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at