rs557897218
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_001122752.2(SERPINI1):āc.684T>Cā(p.Phe228=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,324 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 (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000034 ( 0 hom. )
Consequence
SERPINI1
NM_001122752.2 synonymous
NM_001122752.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.705
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 Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 3-167794627-T-C is Benign according to our data. Variant chr3-167794627-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 466619.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.705 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINI1 | NM_001122752.2 | c.684T>C | p.Phe228= | synonymous_variant | 5/9 | ENST00000446050.7 | |
SERPINI1 | NM_005025.5 | c.684T>C | p.Phe228= | synonymous_variant | 5/9 | ||
SERPINI1 | XM_017006618.3 | c.684T>C | p.Phe228= | synonymous_variant | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINI1 | ENST00000446050.7 | c.684T>C | p.Phe228= | synonymous_variant | 5/9 | 1 | NM_001122752.2 | P1 | |
SERPINI1 | ENST00000295777.9 | c.684T>C | p.Phe228= | synonymous_variant | 5/9 | 1 | P1 | ||
SERPINI1 | ENST00000472747.2 | c.684T>C | p.Phe228= | synonymous_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152030Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250620Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135466
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461176Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726900
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74392
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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 26, 2022 | - - |
Computational scores
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Name
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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