rs372528371
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001122752.2(SERPINI1):āc.286A>Gā(p.Met96Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,613,800 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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. M96T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001122752.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINI1 | NM_001122752.2 | c.286A>G | p.Met96Val | missense_variant | 3/9 | ENST00000446050.7 | |
SERPINI1 | NM_005025.5 | c.286A>G | p.Met96Val | missense_variant | 3/9 | ||
SERPINI1 | XM_017006618.3 | c.286A>G | p.Met96Val | missense_variant | 3/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINI1 | ENST00000446050.7 | c.286A>G | p.Met96Val | missense_variant | 3/9 | 1 | NM_001122752.2 | P1 | |
SERPINI1 | ENST00000295777.9 | c.286A>G | p.Met96Val | missense_variant | 3/9 | 1 | P1 | ||
SERPINI1 | ENST00000472747.2 | c.286A>G | p.Met96Val | missense_variant | 3/5 | 3 | |||
SERPINI1 | ENST00000472941.5 | c.286A>G | p.Met96Val | missense_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152246Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000835 AC: 21AN: 251348Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135838
GnomAD4 exome AF: 0.000302 AC: 442AN: 1461554Hom.: 1 Cov.: 31 AF XY: 0.000303 AC XY: 220AN XY: 727100
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74380
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 28, 2021 | The c.286A>G (p.M96V) alteration is located in exon 3 (coding exon 2) of the SERPINI1 gene. This alteration results from a A to G substitution at nucleotide position 286, causing the methionine (M) at amino acid position 96 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Familial encephalopathy with neuroserpin inclusion bodies Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 02, 2023 | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 96 of the SERPINI1 protein (p.Met96Val). This variant is present in population databases (rs372528371, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SERPINI1-related conditions. ClinVar contains an entry for this variant (Variation ID: 534954). 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 with a negative predictive value of 80%. 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