rs760905589
Positions:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP3_ModeratePP5BS2
The NM_001080508.3(TBX18):c.1570C>T(p.His524Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,457,726 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
TBX18
NM_001080508.3 missense
NM_001080508.3 missense
Scores
6
11
2
Clinical Significance
Conservation
PhyloP100: 7.40
Genes affected
TBX18 (HGNC:11595): (T-box transcription factor 18) This genes codes for a member of an evolutionarily conserved family of transcription factors that plays a crucial role in embryonic development. The family is characterized by the presence of the DNA-binding T-box domain and is divided into five sub-families based on sequence conservation in this domain. The encoded protein belongs to the vertebrate specific Tbx1 sub-family. The protein acts as a transcriptional repressor by antagonizing transcriptional activators in the T-box family. The protein forms homo- or heterodimers with other transcription factors of the T-box family or other transcription factors. [provided by RefSeq, Nov 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.907
PP5
?
Variant 6-84736939-G-A is Pathogenic according to our data. Variant chr6-84736939-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 208528.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
?
High AC in GnomAdExome4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX18 | NM_001080508.3 | c.1570C>T | p.His524Tyr | missense_variant | 8/8 | ENST00000369663.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX18 | ENST00000369663.10 | c.1570C>T | p.His524Tyr | missense_variant | 8/8 | 1 | NM_001080508.3 | P1 | |
TBX18 | ENST00000606784.5 | c.625+1558C>T | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000806 AC: 2AN: 248118Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 133922
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GnomAD4 exome AF: 0.00000480 AC: 7AN: 1457726Hom.: 0 Cov.: 31 AF XY: 0.00000552 AC XY: 4AN XY: 724574
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
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32
ExAC
?
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Congenital anomalies of kidney and urinary tract 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 06, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Benign
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of disorder (P = 0.0684);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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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