rs104893757
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_000306.4(POU1F1):c.71C>T(p.Pro24Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. P24P) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
POU1F1
NM_000306.4 missense
NM_000306.4 missense
Scores
4
13
2
Clinical Significance
Conservation
PhyloP100: 7.18
Genes affected
POU1F1 (HGNC:9210): (POU class 1 homeobox 1) This gene encodes a member of the POU family of transcription factors that regulate mammalian development. The protein regulates expression of several genes involved in pituitary development and hormone expression. Mutations in this genes result in combined pituitary hormone deficiency. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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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, 0.777
PP5
?
Variant 3-87276392-G-A is Pathogenic according to our data. Variant chr3-87276392-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 13605.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POU1F1 | NM_000306.4 | c.71C>T | p.Pro24Leu | missense_variant | 1/6 | ENST00000350375.7 | |
POU1F1 | NM_001122757.3 | c.71C>T | p.Pro24Leu | missense_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POU1F1 | ENST00000350375.7 | c.71C>T | p.Pro24Leu | missense_variant | 1/6 | 1 | NM_000306.4 | P4 | |
POU1F1 | ENST00000344265.8 | c.71C>T | p.Pro24Leu | missense_variant | 1/6 | 5 | A1 | ||
POU1F1 | ENST00000561167.5 | c.71C>T | p.Pro24Leu | missense_variant | 1/5 | 5 | |||
POU1F1 | ENST00000560656.1 | c.71C>T | p.Pro24Leu | missense_variant | 1/4 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Pituitary hormone deficiency, combined, 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 15, 1992 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
M;M;.;.
MutationTaster
Benign
A;A;A
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;.;D
Polyphen
P;B;.;.
Vest4
MutPred
Loss of disorder (P = 0.0481);Loss of disorder (P = 0.0481);Loss of disorder (P = 0.0481);Loss of disorder (P = 0.0481);
MVP
MPC
0.35
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at