rs137876115
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_139076.3(ABRAXAS1):c.364C>T(p.Gln122Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. Q122Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_139076.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABRAXAS1 | NM_139076.3 | c.364C>T | p.Gln122Ter | stop_gained | 5/9 | ENST00000321945.12 | |
ABRAXAS1 | NM_001345962.2 | c.37C>T | p.Gln13Ter | stop_gained | 4/8 | ||
ABRAXAS1 | XR_001741334.3 | n.392C>T | non_coding_transcript_exon_variant | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABRAXAS1 | ENST00000321945.12 | c.364C>T | p.Gln122Ter | stop_gained | 5/9 | 1 | NM_139076.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251138Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135742
GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461544Hom.: 0 Cov.: 31 AF XY: 0.0000454 AC XY: 33AN XY: 727094
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74324
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 14, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 128221). This premature translational stop signal has been observed in individual(s) with head and neck cancer (PMID: 31263571). This variant is present in population databases (rs137876115, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Gln122*) in the ABRAXAS1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ABRAXAS1 cause disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 02, 2020 | Variant summary: FAM175A c.364C>T (p.Gln122X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 3.2e-05 in 251138 control chromosomes, predominantly at a frequency of 6.2e-05 within the Non-Finnish European subpopulation in the gnomAD database. c.364C>T has been reported in the literature in individuals affected with advanced head and neck cancer (Bertelsen_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at