chr11-57611885-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PP3_ModerateBS1_Supporting
The NM_000062.3(SERPING1):c.1198C>T(p.Arg400Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R400H) has been classified as Likely benign.
Frequency
Consequence
NM_000062.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPING1 | NM_000062.3 | c.1198C>T | p.Arg400Cys | missense_variant | 7/8 | ENST00000278407.9 | |
SERPING1 | NM_001032295.2 | c.1198C>T | p.Arg400Cys | missense_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPING1 | ENST00000278407.9 | c.1198C>T | p.Arg400Cys | missense_variant | 7/8 | 1 | NM_000062.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251460Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135902
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461880Hom.: 0 Cov.: 33 AF XY: 0.0000220 AC XY: 16AN XY: 727240
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74310
ClinVar
Submissions by phenotype
Hereditary angioedema type 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 09, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 28, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 400 of the SERPING1 protein (p.Arg400Cys). This variant is present in population databases (rs201363394, gnomAD 0.007%). This missense change has been observed in individual(s) with hereditary angioedema (PMID: 18586324, 18758157, 20864152, 29343682). This variant is also known as p.Arg378Cys. ClinVar contains an entry for this variant (Variation ID: 487525). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SERPING1 protein function. Experimental studies have shown that this missense change affects SERPING1 function (PMID: 20864152, 29343682). 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