8-127416393-GG-AA

Variant names:

• chr8-127416393-GG-AA
• NM_001159542.3:c.527_528delGGinsAA
• POU5F1B p.Gly176Glu

Variant summary

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

The NM_001159542.3(POU5F1B):​c.527_528delGGinsAA​(p.Gly176Glu) variant causes a missense change. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: POU5F1B NM_001159542.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.21
• Publications: 0 publications found

Genes affected

POU5F1B (HGNC:9223): (POU class 5 homeobox 1B) This intronless gene was thought to be a transcribed pseudogene of POU class 5 homeobox 1, however, it has been reported that this gene can encode a functional protein. The encoded protein is nearly the same length as and highly similar to the POU class 5 homeobox 1 transcription factor, has been shown to be a weak transcriptional activator and may play a role in carcinogenesis and eye development. [provided by RefSeq, Apr 2009]

CASC8 (HGNC:45129): (cancer susceptibility 8)

PCAT1 (HGNC:43022): (prostate cancer associated transcript 1) This gene produces a long non-coding RNA that promotes cell proliferation and is upregulated in prostate, colorectal, and other cancers. This RNA negatively regulates the BRCA2 tumor suppressor protein and positively regulates Myc oncoprotein. It contains binding sites for microRNAs, and may act as a sponge for microRNAs that regulate cell growth pathways. [provided by RefSeq, Dec 2017]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159542.3. 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
	POU5F1B	NM_001159542.3	MANE Select	c.527_528delGGinsAA	p.Gly176Glu	missense	N/A	NP_001153014.1	Q06416
	POU5F1B	NM_001395745.1		c.527_528delGGinsAA	p.Gly176Glu	missense	N/A	NP_001382674.1	Q06416
	CASC8	NR_117100.1		n.1176+4435_1176+4436delCCinsTT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1B	ENST00000696633.1	MANE Select	c.527_528delGGinsAA	p.Gly176Glu	missense	N/A	ENSP00000512769.1	Q06416
	CASC8	ENST00000501396.6	TSL:1	n.546+4435_546+4436delCCinsTT		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+4435_1176+4436delCCinsTT		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.2

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: chr8-128428638;