rs1553461069
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_016252.4(BIRC6):c.7976_7979dup(p.Leu2661ThrfsTer13) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
BIRC6
NM_016252.4 frameshift
NM_016252.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.49
Genes affected
BIRC6 (HGNC:13516): (baculoviral IAP repeat containing 6) This gene encodes a protein with a BIR (baculoviral inhibition of apoptosis protein repeat) domain and a UBCc (ubiquitin-conjugating enzyme E2, catalytic) domain. This protein inhibits apoptosis by facilitating the degradation of apoptotic proteins by ubiquitination. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BIRC6 | NM_016252.4 | c.7976_7979dup | p.Leu2661ThrfsTer13 | frameshift_variant | 42/74 | ENST00000421745.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BIRC6 | ENST00000421745.7 | c.7976_7979dup | p.Leu2661ThrfsTer13 | frameshift_variant | 42/74 | 1 | NM_016252.4 | P2 | |
BIRC6 | ENST00000648282.1 | c.7762_7765dup | p.Leu2590ThrfsTer13 | frameshift_variant | 41/58 | ||||
BIRC6 | ENST00000700518.1 | c.7925_7928dup | p.Leu2644ThrfsTer13 | frameshift_variant | 41/73 | A2 | |||
BIRC6 | ENST00000700519.1 | c.7916_7919dup | p.Leu2641ThrfsTer13 | frameshift_variant | 42/74 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 28
GnomAD4 exome
Cov.:
28
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Feb 22, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at