8-127416604-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001159542.3(POU5F1B):c.738G>T(p.Glu246Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000197 in 152,154 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
POU5F1B
NM_001159542.3 missense
NM_001159542.3 missense
Scores
5
11
3
Clinical Significance
Conservation
PhyloP100: 5.36
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]
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.872
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POU5F1B | NM_001159542.3 | c.738G>T | p.Glu246Asp | missense_variant | 1/1 | ENST00000696633.1 | NP_001153014.1 | |
POU5F1B | NM_001395745.1 | c.738G>T | p.Glu246Asp | missense_variant | 2/2 | NP_001382674.1 | ||
CASC8 | NR_117100.1 | n.1176+4225C>A | intron_variant |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000902 AC: 2AN: 221702Hom.: 0 AF XY: 0.00000838 AC XY: 1AN XY: 119400
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1449130Hom.: 0 Cov.: 111 AF XY: 0.00 AC XY: 0AN XY: 719562
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74320
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 14, 2021 | The c.738G>T (p.E246D) alteration is located in exon 1 (coding exon 1) of the POU5F1B gene. This alteration results from a G to T substitution at nucleotide position 738, causing the glutamic acid (E) at amino acid position 246 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D
REVEL
Uncertain
Sift
Uncertain
.;D
Sift4G
Uncertain
.;D
Polyphen
D;D
Vest4
0.33
MutPred
Gain of MoRF binding (P = 0.122);Gain of MoRF binding (P = 0.122);
MVP
0.69
MPC
0.040
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at