rs200281698
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_139076.3(ABRAXAS1):c.1214G>C(p.Arg405Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000651 in 1,612,152 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R405Q) has been classified as Likely benign.
Frequency
Consequence
NM_139076.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABRAXAS1 | NM_139076.3 | c.1214G>C | p.Arg405Pro | missense_variant | 9/9 | ENST00000321945.12 | |
ABRAXAS1 | NM_001345962.2 | c.887G>C | p.Arg296Pro | missense_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABRAXAS1 | ENST00000321945.12 | c.1214G>C | p.Arg405Pro | missense_variant | 9/9 | 1 | NM_139076.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152080Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000152 AC: 38AN: 249830Hom.: 0 AF XY: 0.000163 AC XY: 22AN XY: 135100
GnomAD4 exome AF: 0.0000616 AC: 90AN: 1460072Hom.: 0 Cov.: 30 AF XY: 0.0000647 AC XY: 47AN XY: 726286
GnomAD4 genome ? AF: 0.0000986 AC: 15AN: 152080Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74300
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 14, 2019 | Variant summary: FAM175A c.1214G>C (p.Arg405Pro) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 275768 control chromosomes. The observed variant frequency is approximately 4.53 fold of the estimated maximal expected allele frequency for a pathogenic variant in FAM175A causing Hereditary Breast and Ovarian Cancer phenotype (3.1e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1214G>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at