rs1554996817
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000062.3(SERPING1):c.1264del(p.Ser422LeufsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
SERPING1
NM_000062.3 frameshift
NM_000062.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.676
Genes affected
SERPING1 (HGNC:1228): (serpin family G member 1) This gene encodes a highly glycosylated plasma protein involved in the regulation of the complement cascade. Its encoded protein, C1 inhibitor, inhibits activated C1r and C1s of the first complement component and thus regulates complement activation. It is synthesized in the liver, and its deficiency is associated with hereditary angioneurotic oedema (HANE). Alternative splicing results in multiple transcript variants encoding the same isoform. [provided by RefSeq, May 2020]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 177 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 11-57614337-AT-A is Pathogenic according to our data. Variant chr11-57614337-AT-A is described in ClinVar as [Pathogenic]. Clinvar id is 3950.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-57614337-AT-A is described in Lovd as [Pathogenic]. Variant chr11-57614337-AT-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPING1 | NM_000062.3 | c.1264del | p.Ser422LeufsTer9 | frameshift_variant | 8/8 | ENST00000278407.9 | |
SERPING1 | NM_001032295.2 | c.1264del | p.Ser422LeufsTer9 | frameshift_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPING1 | ENST00000278407.9 | c.1264del | p.Ser422LeufsTer9 | frameshift_variant | 8/8 | 1 | NM_000062.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hereditary angioedema type 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 1991 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at