rs397515503
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_003244.4(TGIF1):c.581T>G(p.Val194Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
TGIF1
NM_003244.4 missense
NM_003244.4 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 1.47
Publications
1 publications found
Genes affected
TGIF1 (HGNC:11776): (TGFB induced factor homeobox 1) The protein encoded by this gene is a member of the three-amino acid loop extension (TALE) superclass of atypical homeodomains. TALE homeobox proteins are highly conserved transcription regulators. This particular homeodomain binds to a previously characterized retinoid X receptor responsive element from the cellular retinol-binding protein II promoter. In addition to its role in inhibiting 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element, the protein is an active transcriptional co-repressor of SMAD2 and may participate in the transmission of nuclear signals during development and in the adult. Mutations in this gene are associated with holoprosencephaly type 4, which is a structural anomaly of the brain. Alternative splicing has been observed at this locus and multiple splice variants encoding distinct isoforms are described. [provided by RefSeq, Jul 2013]
TGIF1 Gene-Disease associations (from GenCC):
- holoprosencephaly 4Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.182237).
BP6
Variant 18-3457702-T-G is Benign according to our data. Variant chr18-3457702-T-G is described in ClinVar as [Benign]. Clinvar id is 65507.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Holoprosencephaly 4 Benign:1
Aug 29, 2013
GeneReviews
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:curation
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
.;.;.;T;.;.;.;.;.;T;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;.;T;T;T;.;T;.;.;T;T;.;.
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;.;.;.;.;.;.;L;.;.;.
PhyloP100
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;.;.;D;T;T;T;T;T;D;T;T;T
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
0.32, 0.013
.;.;.;.;.;B;B;.;.;B;.;.;.
Vest4
MutPred
0.49
.;.;.;.;.;.;.;.;.;Gain of relative solvent accessibility (P = 0.0098);.;.;.;
MVP
MPC
0.59
ClinPred
T
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
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.