rs14175
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_005996.4(TBX3):āc.1095T>Cā(p.His365=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,587,530 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0013 ( 1 hom., cov: 33)
Exomes š: 0.00013 ( 0 hom. )
Consequence
TBX3
NM_005996.4 synonymous
NM_005996.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.463
Genes affected
TBX3 (HGNC:11602): (T-box transcription factor 3) This gene is a member of a phylogenetically 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 developmental processes. This protein is a transcriptional repressor and is thought to play a role in the anterior/posterior axis of the tetrapod forelimb. Mutations in this gene cause ulnar-mammary syndrome, affecting limb, apocrine gland, tooth, hair, and genital development. Alternative splicing of this gene results in three transcript variants encoding different isoforms; however, the full length nature of one variant has not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 12-114674780-A-G is Benign according to our data. Variant chr12-114674780-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 260748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.463 with no splicing effect.
BS2
High AC in GnomAd4 at 192 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX3 | NM_005996.4 | c.1095T>C | p.His365= | synonymous_variant | 6/7 | ENST00000349155.7 | |
TBX3 | NM_016569.4 | c.1155T>C | p.His385= | synonymous_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX3 | ENST00000349155.7 | c.1095T>C | p.His365= | synonymous_variant | 6/7 | 1 | NM_005996.4 | P4 | |
TBX3 | ENST00000257566.7 | c.1155T>C | p.His385= | synonymous_variant | 7/8 | 1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00125 AC: 190AN: 152198Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000277 AC: 57AN: 205750Hom.: 0 AF XY: 0.000160 AC XY: 18AN XY: 112196
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GnomAD4 exome AF: 0.000128 AC: 183AN: 1435214Hom.: 0 Cov.: 32 AF XY: 0.000115 AC XY: 82AN XY: 712744
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GnomAD4 genome AF: 0.00126 AC: 192AN: 152316Hom.: 1 Cov.: 33 AF XY: 0.00117 AC XY: 87AN XY: 74476
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 19, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Ulnar-mammary syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 29, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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