rs863225214

Variant names:

• chr13-72917104-TC-T
• rs863225214
• NM_006346.4:c.1669delC

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_006346.4(PIBF1):​c.1669delC​(p.Leu557PhefsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIBF1 NM_006346.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.20

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]

ACMG classification

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 13-72917104-TC-T is Pathogenic according to our data. Variant chr13-72917104-TC-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 217688.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-72917104-TC-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIBF1	NM_006346.4	c.1669delC	p.Leu557PhefsTer18	frameshift_variant	Exon 13 of 18	ENST00000326291.11	NP_006337.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIBF1	ENST00000326291.11	c.1669delC	p.Leu557PhefsTer18	frameshift_variant	Exon 13 of 18	1	NM_006346.4	ENSP00000317144.6
PIBF1	ENST00000617689.4	c.1669delC	p.Leu557PhefsTer18	frameshift_variant	Exon 13 of 16	1		ENSP00000478697.1
PIBF1	ENST00000615625.1	c.46delC	p.Leu16PhefsTer18	frameshift_variant	Exon 4 of 9	1		ENSP00000483286.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial aplasia of the vermis Pathogenic:1

Jul 13, 2015

UW Hindbrain Malformation Research Program, University of Washington

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs863225214; hg19: chr13-73491242;