rs765761813
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_000488.4(SERPINC1):c.1060C>T(p.Arg354Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,658 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. R354H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000488.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINC1 | NM_000488.4 | c.1060C>T | p.Arg354Cys | missense_variant | 5/7 | ENST00000367698.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINC1 | ENST00000367698.4 | c.1060C>T | p.Arg354Cys | missense_variant | 5/7 | 1 | NM_000488.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461472Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 726978
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74338
ClinVar
Submissions by phenotype
Hereditary antithrombin deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 22, 2018 | This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SERPINC1-related disease. This sequence change replaces arginine with cysteine at codon 354 of the SERPINC1 protein (p.Arg354Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at