rs1553774750
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_001122752.2(SERPINI1):c.573G>A(p.Lys191=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SERPINI1
NM_001122752.2 synonymous
NM_001122752.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.24
Genes affected
SERPINI1 (HGNC:8943): (serpin family I member 1) This gene encodes a member of the serpin superfamily of serine proteinase inhibitors. The protein is primarily secreted by axons in the brain, and preferentially reacts with and inhibits tissue-type plasminogen activator. It is thought to play a role in the regulation of axonal growth and the development of synaptic plasticity. Mutations in this gene result in familial encephalopathy with neuroserpin inclusion bodies (FENIB), which is a dominantly inherited form of familial encephalopathy and epilepsy characterized by the accumulation of mutant neuroserpin polymers. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
Variant 3-167792681-G-A is Benign according to our data. Variant chr3-167792681-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 534959.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.24 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINI1 | NM_001122752.2 | c.573G>A | p.Lys191= | synonymous_variant | 4/9 | ENST00000446050.7 | |
SERPINI1 | NM_005025.5 | c.573G>A | p.Lys191= | synonymous_variant | 4/9 | ||
SERPINI1 | XM_017006618.3 | c.573G>A | p.Lys191= | synonymous_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINI1 | ENST00000446050.7 | c.573G>A | p.Lys191= | synonymous_variant | 4/9 | 1 | NM_001122752.2 | P1 | |
SERPINI1 | ENST00000295777.9 | c.573G>A | p.Lys191= | synonymous_variant | 4/9 | 1 | P1 | ||
SERPINI1 | ENST00000472747.2 | c.573G>A | p.Lys191= | synonymous_variant | 4/5 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461584Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727096
GnomAD4 exome
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1
AN:
1461584
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31
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0
AN XY:
727096
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial encephalopathy with neuroserpin inclusion bodies Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 17, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at