17-61456593-G-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001321120.2(TBX4):c.103G>T(p.Ala35Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000982 in 1,527,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A35V) has been classified as Likely benign.
Frequency
Consequence
NM_001321120.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TBX4 | ENST00000644296.1 | c.103G>T | p.Ala35Ser | missense_variant | 2/9 | NM_001321120.2 | ENSP00000495986.1 | |||
TBX4 | ENST00000240335.1 | c.103G>T | p.Ala35Ser | missense_variant | 1/8 | 1 | ENSP00000240335.1 | |||
TBX4 | ENST00000642491.1 | c.103G>T | p.Ala35Ser | missense_variant | 1/8 | ENSP00000495714.1 | ||||
TBX4 | ENST00000589003.5 | c.-125-31G>T | intron_variant | 3 | ENSP00000467588.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151994Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000872 AC: 12AN: 1375820Hom.: 0 Cov.: 32 AF XY: 0.00000737 AC XY: 5AN XY: 678282
GnomAD4 genome AF: 0.0000197 AC: 3AN: 151994Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74234
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 11, 2024 | The c.103G>T (p.A35S) alteration is located in exon 1 (coding exon 1) of the TBX4 gene. This alteration results from a G to T substitution at nucleotide position 103, causing the alanine (A) at amino acid position 35 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at