16-30086333-A-G
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_004608.4(TBX6):c.1203T>C(p.Ala401=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000386 in 1,605,204 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 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000039 ( 0 hom. )
Consequence
TBX6
NM_004608.4 synonymous
NM_004608.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.146
Genes affected
TBX6 (HGNC:11605): (T-box transcription factor 6) 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. Knockout studies in mice indicate that this gene is important for specification of paraxial mesoderm structures. [provided by RefSeq, Aug 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 16-30086333-A-G is Benign according to our data. Variant chr16-30086333-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 743868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.146 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX6 | NM_004608.4 | c.1203T>C | p.Ala401= | synonymous_variant | 9/9 | ENST00000395224.7 | |
TBX6 | XM_011545926.4 | c.1203T>C | p.Ala401= | synonymous_variant | 9/9 | ||
TBX6 | XM_047434551.1 | c.1203T>C | p.Ala401= | synonymous_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX6 | ENST00000395224.7 | c.1203T>C | p.Ala401= | synonymous_variant | 9/9 | 1 | NM_004608.4 | P1 | |
TBX6 | ENST00000279386.6 | c.1203T>C | p.Ala401= | synonymous_variant | 8/8 | 1 | P1 | ||
TBX6 | ENST00000567664.5 | c.*337T>C | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 151982Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000195 AC: 46AN: 235490Hom.: 0 AF XY: 0.000116 AC XY: 15AN XY: 129170
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GnomAD4 exome AF: 0.0000392 AC: 57AN: 1453222Hom.: 0 Cov.: 34 AF XY: 0.0000249 AC XY: 18AN XY: 723240
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 151982Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74240
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 19, 2023 | - - |
TBX6-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 29, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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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