3-93873875-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000313.4(PROS1):c.*370G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 240,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
PROS1
NM_000313.4 3_prime_UTR
NM_000313.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.14
Genes affected
PROS1 (HGNC:9456): (protein S) This gene encodes a vitamin K-dependent plasma protein that functions as a cofactor for the anticoagulant protease, activated protein C (APC) to inhibit blood coagulation. It is found in plasma in both a free, functionally active form and also in an inactive form complexed with C4b-binding protein. Mutations in this gene result in autosomal dominant hereditary thrombophilia. An inactive pseudogene of this locus is located at an adjacent region on chromosome 3. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PROS1 | NM_000313.4 | c.*370G>A | 3_prime_UTR_variant | 15/15 | ENST00000394236.9 | NP_000304.2 | ||
| PROS1 | NM_001314077.2 | c.*370G>A | 3_prime_UTR_variant | 16/16 | NP_001301006.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PROS1 | ENST00000394236.9 | c.*370G>A | 3_prime_UTR_variant | 15/15 | 1 | NM_000313.4 | ENSP00000377783 | P1 |
Frequencies
GnomAD3 genomes 0.000164 AC: 25AN: 152028Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.0000338 AC: 3AN: 88754Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 47356
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GnomAD4 genome 0.000164 AC: 25AN: 152146Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74380
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Thrombophilia due to protein S deficiency, autosomal dominant Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at