22-41382151-C-T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_003216.4(TEF):c.107C>T(p.Pro36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TEF
NM_003216.4 missense
NM_003216.4 missense
Scores
3
12
4
Clinical Significance
Conservation
PhyloP100: 2.44
Publications
0 publications found
Genes affected
TEF (HGNC:11722): (TEF transcription factor, PAR bZIP family member) This gene encodes a member of the PAR (proline and acidic amino acid-rich) subfamily of basic region/leucine zipper (bZIP) transcription factors. It is expressed in a broad range of cells and tissues in adult animals, however, during embryonic development, TEF expression appears to be restricted to the developing anterior pituitary gland, coincident with the appearance of thyroid-stimulating hormone, beta (TSHB). Indeed, TEF can bind to, and transactivate the TSHB promoter. It shows homology (in the functional domains) with other members of the PAR-bZIP subfamily of transcription factors, which include albumin D box-binding protein (DBP), human hepatic leukemia factor (HLF) and chicken vitellogenin gene-binding protein (VBP); VBP is considered the chicken homologue of TEF. Different members of the subfamily can readily form heterodimers, and share DNA-binding, and transcriptional regulatory properties. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TEF | NM_003216.4 | c.107C>T | p.Pro36Leu | missense_variant | Exon 1 of 4 | ENST00000266304.9 | NP_003207.1 | |
| TEF | NM_001145398.3 | c.68-5200C>T | intron_variant | Intron 1 of 3 | NP_001138870.1 | |||
| LOC105373042 | XR_938271.3 | n.-240G>A | upstream_gene_variant |
Ensembl
Frequencies
GnomAD3 genomes 0.00000659 AC: 1AN: 151824Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151824
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1089410Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 515546
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1089410
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
515546
African (AFR)
AF:
AC:
0
AN:
23314
American (AMR)
AF:
AC:
0
AN:
9646
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
14406
East Asian (EAS)
AF:
AC:
0
AN:
27004
South Asian (SAS)
AF:
AC:
0
AN:
20074
European-Finnish (FIN)
AF:
AC:
0
AN:
21466
Middle Eastern (MID)
AF:
AC:
0
AN:
3878
European-Non Finnish (NFE)
AF:
AC:
0
AN:
925518
Other (OTH)
AF:
AC:
0
AN:
44104
GnomAD4 genome 0.00000659 AC: 1AN: 151824Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74166 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
151824
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74166
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41352
American (AMR)
AF:
AC:
0
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5146
South Asian (SAS)
AF:
AC:
1
AN:
4816
European-Finnish (FIN)
AF:
AC:
0
AN:
10592
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67866
Other (OTH)
AF:
AC:
0
AN:
2084
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Jun 06, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.107C>T (p.P36L) alteration is located in exon 1 (coding exon 1) of the TEF gene. This alteration results from a C to T substitution at nucleotide position 107, causing the proline (P) at amino acid position 36 to be replaced by a leucine (L). 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
Uncertain
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of helix (P = 0.0496);
MVP
MPC
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
Publications
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