1-11022290-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 7P and 4B. PM1PM2PM5PP2BS2
The NM_007375.4(TARDBP):āc.881G>Cā(p.Gly294Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G294V) has been classified as Pathogenic.
Frequency
Consequence
NM_007375.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TARDBP | NM_007375.4 | c.881G>C | p.Gly294Ala | missense_variant | 6/6 | ENST00000240185.8 | NP_031401.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TARDBP | ENST00000240185.8 | c.881G>C | p.Gly294Ala | missense_variant | 6/6 | 1 | NM_007375.4 | ENSP00000240185 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461670Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727144
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Amyotrophic lateral sclerosis type 10 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2009 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 16, 2022 | The p.G294A variant (also known as c.881G>C), located in coding exon 5 of the TARDBP gene, results from a G to C substitution at nucleotide position 881. The glycine at codon 294 is replaced by alanine, an amino acid with similar properties. This alteration has been detected in an individual with sporadic, late-onset amyotrophic lateral sclerosis (Sreedharan J et al. Science, 2008 Mar;319:1668-72). This amino acid position is well conserved in available vertebrate species; however, alanine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at