9-135562864-CT-TC

Variant names:

• chr9-135562864-CT-TC
• NM_002571.4:c.281_282delCTinsTC
• PAEP p.Thr94Ile

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002571.4(PAEP):​c.281_282delCTinsTC​(p.Thr94Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: PAEP NM_002571.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.552
• Publications: 0 publications found

Genes affected

PAEP (HGNC:8573): (progestagen associated endometrial protein) This gene is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The encoded glycoprotein has been previously referred to as pregnancy-associated endometrial alpha-2-globulin, placental protein 14, and glycodelin, but has been officially named progestagen-associated endometrial protein. Three distinct forms, with identical protein backbones but different glycosylation profiles, are found in amniotic fluid, follicular fluid and seminal plasma of the reproductive system. These glycoproteins have distinct and essential roles in regulating a uterine environment suitable for pregnancy and in the timing and occurrence of the appropriate sequence of events in the fertilization process. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002571.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAEP	NM_002571.4	MANE Select	c.281_282delCTinsTC	p.Thr94Ile	missense	N/A	NP_002562.2	P09466-1
	PAEP	NM_001018049.3		c.281_282delCTinsTC	p.Thr94Ile	missense	N/A	NP_001018059.1	P09466-1
	PAEP	NM_001018048.2		c.215_216delCTinsTC	p.Thr72Ile	missense	N/A	NP_001018058.1	P09466-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAEP	ENST00000479141.6	TSL:1 MANE Select	c.281_282delCTinsTC	p.Thr94Ile	missense	N/A	ENSP00000417898.1	P09466-1
	PAEP	ENST00000277508.9	TSL:1	c.281_282delCTinsTC	p.Thr94Ile	missense	N/A	ENSP00000277508.5	P09466-1
	PAEP	ENST00000371766.6	TSL:1	c.281_282delCTinsTC	p.Thr94Ile	missense	N/A	ENSP00000360831.1	P09466-1

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.55

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-138454710;