rs565325519
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000313.4(PROS1):c.1247C>T(p.Pro416Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000973 in 1,613,568 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P416P) has been classified as Likely benign.
Frequency
Consequence
NM_000313.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PROS1 | NM_000313.4 | c.1247C>T | p.Pro416Leu | missense_variant | 11/15 | ENST00000394236.9 | |
PROS1 | NM_001314077.2 | c.1343C>T | p.Pro448Leu | missense_variant | 12/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PROS1 | ENST00000394236.9 | c.1247C>T | p.Pro416Leu | missense_variant | 11/15 | 1 | NM_000313.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000856 AC: 13AN: 151940Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251354Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135860
GnomAD4 exome AF: 0.0000978 AC: 143AN: 1461510Hom.: 1 Cov.: 31 AF XY: 0.000111 AC XY: 81AN XY: 727070
GnomAD4 genome ? AF: 0.0000921 AC: 14AN: 152058Hom.: 1 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74332
ClinVar
Submissions by phenotype
Thrombophilia due to protein S deficiency, autosomal dominant;C3281092:Thrombophilia due to protein S deficiency, autosomal recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 26, 2021 | - - |
Thrombophilia due to protein S deficiency, autosomal recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 02, 2021 | This sequence change replaces proline with leucine at codon 416 of the PROS1 protein (p.Pro416Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs565325519, ExAC 0.02%). This missense change has been observed in individual(s) with protein S deficiency (PMID: 26466767). ClinVar contains an entry for this variant (Variation ID: 216419). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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