rs7614835
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000313.4(PROS1):c.119G>T(p.Arg40Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00131 in 1,614,090 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R40H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000313.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PROS1 | NM_000313.4 | c.119G>T | p.Arg40Leu | missense_variant | 2/15 | ENST00000394236.9 | |
PROS1 | NM_001314077.2 | c.215G>T | p.Arg72Leu | missense_variant | 3/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PROS1 | ENST00000394236.9 | c.119G>T | p.Arg40Leu | missense_variant | 2/15 | 1 | NM_000313.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00703 AC: 1070AN: 152144Hom.: 11 Cov.: 32
GnomAD3 exomes AF: 0.00168 AC: 423AN: 251362Hom.: 5 AF XY: 0.00105 AC XY: 142AN XY: 135864
GnomAD4 exome AF: 0.000717 AC: 1048AN: 1461828Hom.: 4 Cov.: 31 AF XY: 0.000602 AC XY: 438AN XY: 727214
GnomAD4 genome ? AF: 0.00703 AC: 1070AN: 152262Hom.: 11 Cov.: 32 AF XY: 0.00633 AC XY: 471AN XY: 74448
ClinVar
Submissions by phenotype
Thrombophilia due to protein S deficiency, autosomal dominant Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Sep 08, 2022 | BS1, PM1, PS3 - |
Protein S deficiency disease Uncertain:1
Uncertain significance, criteria provided, single submitter | research | NIHR Bioresource Rare Diseases, University of Cambridge | Feb 01, 2019 | - - |
PROS1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 22, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Thrombophilia due to protein S deficiency, autosomal recessive Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at