chr11-102324519-G-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001165.5(BIRC3):c.10G>C(p.Val4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,610,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000051 ( 0 hom. )
Consequence
BIRC3
NM_001165.5 missense
NM_001165.5 missense
Scores
16
Clinical Significance
Conservation
PhyloP100: 0.247
Genes affected
BIRC3 (HGNC:591): (baculoviral IAP repeat containing 3) This gene encodes a member of the IAP family of proteins that inhibit apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, probably by interfering with activation of ICE-like proteases. The encoded protein inhibits apoptosis induced by serum deprivation but does not affect apoptosis resulting from exposure to menadione, a potent inducer of free radicals. It contains 3 baculovirus IAP repeats and a ring finger domain. Transcript variants encoding the same isoform have been identified. [provided by RefSeq, Aug 2011]
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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=0.04177755).
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BIRC3 | NM_001165.5 | c.10G>C | p.Val4Leu | missense_variant | 2/9 | ENST00000263464.9 | |
BIRC3 | NM_182962.3 | c.10G>C | p.Val4Leu | missense_variant | 3/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BIRC3 | ENST00000263464.9 | c.10G>C | p.Val4Leu | missense_variant | 2/9 | 1 | NM_001165.5 | P1 | |
ENST00000673690.1 | n.96-1747C>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000804 AC: 2AN: 248894Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134498
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GnomAD4 exome AF: 0.0000507 AC: 74AN: 1458644Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 39AN XY: 725424
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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 | May 09, 2022 | The c.10G>C (p.V4L) alteration is located in exon 1 (coding exon 1) of the BIRC3 gene. This alteration results from a G to C substitution at nucleotide position 10, causing the valine (V) at amino acid position 4 to be replaced by a leucine (L). 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
Benign
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
N;N
PrimateAI
Benign
T
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MutPred
Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);
MVP
MPC
0.26
ClinPred
T
GERP RS
Varity_R
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