rs960772904
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_139076.3(ABRAXAS1):āc.832A>Gā(p.Ile278Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 1,599,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I278S) has been classified as Uncertain significance.
Frequency
Consequence
NM_139076.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABRAXAS1 | NM_139076.3 | c.832A>G | p.Ile278Val | missense_variant | 9/9 | ENST00000321945.12 | |
ABRAXAS1 | NM_001345962.2 | c.505A>G | p.Ile169Val | missense_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABRAXAS1 | ENST00000321945.12 | c.832A>G | p.Ile278Val | missense_variant | 9/9 | 1 | NM_139076.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152134Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000426 AC: 1AN: 234824Hom.: 0 AF XY: 0.00000786 AC XY: 1AN XY: 127276
GnomAD4 exome AF: 0.00000276 AC: 4AN: 1447550Hom.: 0 Cov.: 32 AF XY: 0.00000278 AC XY: 2AN XY: 719356
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152134Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74302
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 18, 2023 | The p.I278V variant (also known as c.832A>G), located in coding exon 9 of the FAM175A gene, results from an A to G substitution at nucleotide position 832. The isoleucine at codon 278 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 24, 2021 | In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces isoleucine with valine at codon 278 of the FAM175A protein (p.Ile278Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FAM175A-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at