11-102325089-T-G

Position:

• chr11-102325089-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001165.5(BIRC3):​c.580T>G​(p.Phe194Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BIRC3 NM_001165.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.84

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]

ENSG00000288528 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.924

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIRC3	NM_001165.5	c.580T>G	p.Phe194Val	missense_variant	2/9	ENST00000263464.9	NP_001156.1
BIRC3	NM_182962.3	c.580T>G	p.Phe194Val	missense_variant	3/10		NP_892007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIRC3	ENST00000263464.9	c.580T>G	p.Phe194Val	missense_variant	2/9	1	NM_001165.5	ENSP00000263464.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2023

The c.580T>G (p.F194V) alteration is located in exon 1 (coding exon 1) of the BIRC3 gene. This alteration results from a T to G substitution at nucleotide position 580, causing the phenylalanine (F) at amino acid position 194 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D;D;D
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D;.;.
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.92	D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Pathogenic	4.5	H;H;H
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-4.1	.;D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0020	.;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.63
MutPred		0.87		Gain of phosphorylation at Y195 (P = 0.1171);Gain of phosphorylation at Y195 (P = 0.1171);Gain of phosphorylation at Y195 (P = 0.1171);
MVP		0.65
MPC		1.1
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.62
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-102195820;