rs746335599
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3BP6BS1BS2
The NM_001379200.1(TBX1):c.1426_1455del(p.Ala476_Ala485del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,469,864 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A472A) has been classified as Likely benign.
Frequency
Consequence
NM_001379200.1 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX1 | NM_001379200.1 | c.1426_1455del | p.Ala476_Ala485del | inframe_deletion | 7/7 | ENST00000649276.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX1 | ENST00000649276.2 | c.1426_1455del | p.Ala476_Ala485del | inframe_deletion | 7/7 | NM_001379200.1 | A2 | ||
TBX1 | ENST00000332710.8 | c.1399_1428del | p.Ala467_Ala476del | inframe_deletion | 9/9 | 1 | P2 | ||
TBX1 | ENST00000329705.11 | c.1009+776_1009+805del | intron_variant | 1 | A2 | ||||
TBX1 | ENST00000359500.7 | c.1009+776_1009+805del | intron_variant | 1 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000727 AC: 11AN: 151264Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000302 AC: 25AN: 82690Hom.: 1 AF XY: 0.000375 AC XY: 18AN XY: 48000
GnomAD4 exome AF: 0.0000690 AC: 91AN: 1318600Hom.: 2 AF XY: 0.0000767 AC XY: 50AN XY: 651514
GnomAD4 genome AF: 0.0000727 AC: 11AN: 151264Hom.: 0 Cov.: 33 AF XY: 0.0000948 AC XY: 7AN XY: 73844
ClinVar
Submissions by phenotype
DiGeorge syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | This variant, c.1399_1428del, results in the deletion of 10 amino acid(s) of the TBX1 protein (p.Ala467_Ala476del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs746335599, gnomAD 0.05%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with TBX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 518565). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 04, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at