Variant 13-72783587-C-T details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.84

Variant links:

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]

PIBF1 links:

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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 linkuse as main transcript	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 linkuse as main transcript	c.118C>T	p.Arg40Ter	stop_gained	2/18	1	NM_006346.4	P1	Q8WXW3-1
PIBF1	ENST00000617689.4 linkuse as main transcript	c.118C>T	p.Arg40Ter	stop_gained	2/16	1
PIBF1	ENST00000615625.1 linkuse as main transcript	c.-262+1238C>T		intron_variant		1			Q8WXW3-2
PIBF1	ENST00000489797.1 linkuse as main transcript	n.196+1238C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251366

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461676

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.61

BayesDel_noAF

Pathogenic

0.56

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.95

MutationTaster

Benign

1.0

Vest4

0.59

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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