3-93879279-C-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM1BP4_StrongBP6BS1BS2
The NM_000313.4(PROS1):c.1528G>A(p.Val510Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00064 in 1,614,028 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000313.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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PROS1 | NM_000313.4 | c.1528G>A | p.Val510Met | missense_variant | Exon 13 of 15 | ENST00000394236.9 | NP_000304.2 | |
PROS1 | NM_001314077.2 | c.1624G>A | p.Val542Met | missense_variant | Exon 14 of 16 | NP_001301006.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00350 AC: 533AN: 152142Hom.: 5 Cov.: 32
GnomAD3 exomes AF: 0.000879 AC: 221AN: 251446Hom.: 3 AF XY: 0.000633 AC XY: 86AN XY: 135894
GnomAD4 exome AF: 0.000341 AC: 499AN: 1461768Hom.: 1 Cov.: 31 AF XY: 0.000296 AC XY: 215AN XY: 727190
GnomAD4 genome AF: 0.00351 AC: 534AN: 152260Hom.: 5 Cov.: 32 AF XY: 0.00337 AC XY: 251AN XY: 74452
ClinVar
Submissions by phenotype
Thrombophilia due to protein S deficiency, autosomal dominant Uncertain:1Benign:2Other:1
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not provided Uncertain:2Benign:1
PS4, BS2 -
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BS1, BS2, PM1_supporting, PS3, PS4_moderate -
Protein S deficiency disease Pathogenic:1
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PROS1-related disorder Benign:1
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 dominant;C3281092:Thrombophilia due to protein S deficiency, autosomal recessive Benign:1
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Thrombophilia due to protein S deficiency, autosomal recessive Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at