2-32415105-A-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_016252.4(BIRC6):c.1814A>G(p.Gln605Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000781 in 1,613,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000098 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000076 ( 0 hom. )
Consequence
BIRC6
NM_016252.4 missense
NM_016252.4 missense
Scores
4
12
Clinical Significance
Conservation
PhyloP100: 3.67
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 Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.05771151).
BS2
?
High AC in GnomAd at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BIRC6 | NM_016252.4 | c.1814A>G | p.Gln605Arg | missense_variant | 10/74 | ENST00000421745.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BIRC6 | ENST00000421745.7 | c.1814A>G | p.Gln605Arg | missense_variant | 10/74 | 1 | NM_016252.4 | P2 | |
BIRC6 | ENST00000700518.1 | c.1814A>G | p.Gln605Arg | missense_variant | 10/73 | A2 | |||
BIRC6 | ENST00000700519.1 | c.1814A>G | p.Gln605Arg | missense_variant | 10/74 | ||||
BIRC6 | ENST00000648282.1 | c.1652A>G | p.Gln551Arg | missense_variant | 10/58 |
Frequencies
GnomAD3 genomes ? AF: 0.0000985 AC: 15AN: 152210Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000132 AC: 33AN: 250916Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135594
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GnomAD4 exome AF: 0.0000759 AC: 111AN: 1461588Hom.: 0 Cov.: 31 AF XY: 0.0000811 AC XY: 59AN XY: 727076
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GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.0000805 AC XY: 6AN XY: 74498
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 26, 2022 | The c.1814A>G (p.Q605R) alteration is located in exon 10 (coding exon 10) of the BIRC6 gene. This alteration results from a A to G substitution at nucleotide position 1814, causing the glutamine (Q) at amino acid position 605 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at