rs529527925
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_001365276.2(TNXB):āc.10045G>Cā(p.Ala3349Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,474,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3349T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001365276.2 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNXB | NM_001365276.2 | c.10045G>C | p.Ala3349Pro | missense_variant, splice_region_variant | 29/44 | ENST00000644971.2 | |
TNXB | NM_019105.8 | c.10039G>C | p.Ala3347Pro | missense_variant, splice_region_variant | 29/44 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNXB | ENST00000644971.2 | c.10045G>C | p.Ala3349Pro | missense_variant, splice_region_variant | 29/44 | NM_001365276.2 | |||
TNXB | ENST00000647633.1 | c.10786G>C | p.Ala3596Pro | missense_variant, splice_region_variant | 30/45 | P1 | |||
TNXB | ENST00000375244.7 | c.10045G>C | p.Ala3349Pro | missense_variant, splice_region_variant | 29/44 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152196Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000552 AC: 93AN: 168606Hom.: 0 AF XY: 0.000600 AC XY: 54AN XY: 90034
GnomAD4 exome AF: 0.000123 AC: 163AN: 1322560Hom.: 0 Cov.: 32 AF XY: 0.000137 AC XY: 88AN XY: 643782
GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152314Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21AN XY: 74474
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 18, 2021 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | TNXB: BP4 - |
TNXB-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 27, 2021 | 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). - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 16, 2023 | 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