chr17-78223522-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001168.3(BIRC5):c.397C>T(p.Arg133Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000974 in 1,612,420 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. 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. R133H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001168.3 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 |
---|---|---|---|---|---|---|---|
BIRC5 | NM_001168.3 | c.397C>T | p.Arg133Cys | missense_variant | 4/4 | ENST00000350051.8 | |
BIRC5 | NM_001012271.2 | c.466C>T | p.Arg156Cys | missense_variant | 5/5 | ||
BIRC5 | NM_001012270.2 | c.279C>T | p.Ala93= | synonymous_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BIRC5 | ENST00000350051.8 | c.397C>T | p.Arg133Cys | missense_variant | 4/4 | 1 | NM_001168.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000400 AC: 10AN: 249830Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135124
GnomAD4 exome AF: 0.000103 AC: 150AN: 1460188Hom.: 0 Cov.: 34 AF XY: 0.0000950 AC XY: 69AN XY: 726282
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74366
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 23, 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