chr11-57598272-T-G
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate
The NM_000062.3(SERPING1):c.2T>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Consequence
SERPING1
NM_000062.3 start_lost
NM_000062.3 start_lost
Scores
8
5
3
Clinical Significance
Conservation
PhyloP100: 0.566
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 14 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_000062.3 (SERPING1) was described as [Pathogenic] in ClinVar as 626352
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 11-57598272-T-G is Pathogenic according to our data. Variant chr11-57598272-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 2910260.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-57598272-T-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPING1 | NM_000062.3 | c.2T>G | p.Met1? | start_lost | 2/8 | ENST00000278407.9 | |
SERPING1 | NM_001032295.2 | c.2T>G | p.Met1? | start_lost | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPING1 | ENST00000278407.9 | c.2T>G | p.Met1? | start_lost | 2/8 | 1 | NM_000062.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 05, 2023 | For these reasons, this variant has been classified as Pathogenic. Disruption of the initiator codon has been observed in individuals with hereditary angioedema (PMID: 18535392, 21832835, 24456027; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the SERPING1 mRNA. The next in-frame methionine is located at codon 53. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;T;.;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;T;D;D;T;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D;D
PROVEAN
Benign
N;N;D;N;N;N;.
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;D;D;.
Sift4G
Pathogenic
D;D;D;D;D;D;D
Polyphen
0.98, 0.99
.;D;.;.;.;D;.
Vest4
0.82, 0.76, 0.80, 0.68, 0.60
MutPred
0.47
.;.;Loss of catalytic residue at M35 (P = 0.0189);.;.;Loss of catalytic residue at M35 (P = 0.0189);.;
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
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
Publications
No publications associated with this variant yet.