chr13-72792525-G-A

Position:

• chr13-72792525-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006346.4(PIBF1):​c.331G>A​(p.Ala111Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PIBF1 NM_006346.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.64

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034766227).
• BP6: Variant 13-72792525-G-A is Benign according to our data. Variant chr13-72792525-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2331545.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.331G>A	p.Ala111Thr	missense_variant	3/18	ENST00000326291.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIBF1	ENST00000326291.11	c.331G>A	p.Ala111Thr	missense_variant	3/18	1	NM_006346.4	P1
PIBF1	ENST00000617689.4	c.331G>A	p.Ala111Thr	missense_variant	3/16	1
PIBF1	ENST00000615625.1	c.-262+10176G>A		intron_variant		1
PIBF1	ENST00000489797.1	n.275G>A		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1397358 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 694352

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	16
DANN	Benign	0.67
DEOGEN2	Benign	0.0029	T;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.035	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.22	N;.
MutationTaster	Benign	0.95	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.10	N;.
REVEL	Benign	0.14
Sift	Benign	0.56	T;.
Sift4G	Benign	0.58	T;T
Polyphen		0.0	B;.
Vest4		0.026
MutPred		0.12		Gain of phosphorylation at A111 (P = 0.0932);Gain of phosphorylation at A111 (P = 0.0932);
MVP		0.055
MPC		0.046
ClinPred		0.45	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.022
gMVP		0.038

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-73366663;