chr13-72783587-C-T
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_006346.4(PIBF1):c.118C>T(p.Arg40Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,461,676 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
PIBF1
NM_006346.4 stop_gained
NM_006346.4 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 1.84
Genes affected
PIBF1 (HGNC:23352): (progesterone immunomodulatory binding factor 1) This gene encodes a protein that is induced by the steroid hormone progesterone and plays a role in the maintenance of pregnancy. The encoded protein regulates multiple facets of the immune system to promote normal pregnancy including cytokine synthesis, natural killer (NK) cell activity, and arachidonic acid metabolism. Low serum levels of this protein have been associated with spontaneous pre-term labor in humans. This protein may promote the proliferation, migration and invasion of glioma. [provided by RefSeq, Mar 2017]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 13-72783587-C-T is Pathogenic according to our data. Variant chr13-72783587-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 1979240.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIBF1 | NM_006346.4 | c.118C>T | p.Arg40Ter | stop_gained | 2/18 | ENST00000326291.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIBF1 | ENST00000326291.11 | c.118C>T | p.Arg40Ter | stop_gained | 2/18 | 1 | NM_006346.4 | P1 | |
PIBF1 | ENST00000617689.4 | c.118C>T | p.Arg40Ter | stop_gained | 2/16 | 1 | |||
PIBF1 | ENST00000615625.1 | c.-262+1238C>T | intron_variant | 1 | |||||
PIBF1 | ENST00000489797.1 | n.196+1238C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251366Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135868
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GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461676Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727142
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | This sequence change creates a premature translational stop signal (p.Arg40*) in the PIBF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PIBF1 are known to be pathogenic (PMID: 28688840, 33004012). This variant is present in population databases (rs770532605, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with PIBF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1979240). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at