chr2-161416666-G-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_006593.4(TBR1):c.256G>T(p.Val86Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00026 ( 0 hom. )
Consequence
TBR1
NM_006593.4 missense
NM_006593.4 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 7.26
Genes affected
TBR1 (HGNC:11590): (T-box brain transcription factor 1) This gene is a member of a conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of numerous developmental processes. In mouse, the ortholog of this gene is expressed in the cerebral cortex, hippocampus, amygdala and olfactory bulb and is thought to play an important role in neuronal migration and axonal projection. In mouse, the C-terminal region of this protein was found to be necessary and sufficient for association with the guanylate kinase domain of calcium/calmodulin-dependent serine protein kinase. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.22176623).
BP6
Variant 2-161416666-G-T is Benign according to our data. Variant chr2-161416666-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3024658.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBR1 | NM_006593.4 | c.256G>T | p.Val86Phe | missense_variant | 1/6 | ENST00000389554.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBR1 | ENST00000389554.8 | c.256G>T | p.Val86Phe | missense_variant | 1/6 | 1 | NM_006593.4 | P1 | |
TBR1 | ENST00000463544.1 | n.336G>T | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152192Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000994 AC: 25AN: 251418Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135894
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GnomAD4 exome AF: 0.000255 AC: 373AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.000239 AC XY: 174AN XY: 727246
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GnomAD4 genome AF: 0.000131 AC: 20AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74354
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | TBR1: PP2, BS1 - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Benign
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
D
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
ClinPred
T
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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