12-114408030-C-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_000192.3(TBX5):c.-255G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 985,440 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 Uncertain significance (★).
Frequency
Consequence
NM_000192.3 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TBX5 | NM_000192.3 | c.-255G>T | 5_prime_UTR_variant | Exon 1 of 9 | NP_000183.2 | |||
TBX5 | NM_080717.4 | c.-220G>T | upstream_gene_variant | NP_542448.1 | ||||
TBX5 | XM_017019912.2 | c.-1692G>T | upstream_gene_variant | XP_016875401.1 | ||||
TBX5-AS1 | NR_038440.1 | n.-165C>A | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TBX5 | ENST00000310346.8 | c.-255G>T | 5_prime_UTR_variant | Exon 1 of 9 | 1 | ENSP00000309913.4 | ||||
TBX5 | ENST00000349716.9 | c.-220G>T | 5_prime_UTR_variant | Exon 1 of 8 | 1 | ENSP00000337723.5 | ||||
TBX5-AS1 | ENST00000528549.3 | n.-104C>A | upstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.000992 AC: 151AN: 152206Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00202 AC: 1687AN: 833116Hom.: 1 Cov.: 29 AF XY: 0.00214 AC XY: 824AN XY: 384722
GnomAD4 genome AF: 0.000991 AC: 151AN: 152324Hom.: 0 Cov.: 33 AF XY: 0.000819 AC XY: 61AN XY: 74482
ClinVar
Submissions by phenotype
Holt-Oram syndrome Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at