11-102324996-C-T

Position:

• chr11-102324996-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001165.5(BIRC3):​c.487C>T​(p.His163Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,878 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BIRC3 NM_001165.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.898

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08558479).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIRC3	NM_001165.5	c.487C>T	p.His163Tyr	missense_variant	2/9	ENST00000263464.9	NP_001156.1
BIRC3	NM_182962.3	c.487C>T	p.His163Tyr	missense_variant	3/10		NP_892007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIRC3	ENST00000263464.9	c.487C>T	p.His163Tyr	missense_variant	2/9	1	NM_001165.5	ENSP00000263464.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

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

Nov 07, 2024

The c.487C>T (p.H163Y) alteration is located in exon 1 (coding exon 1) of the BIRC3 gene. This alteration results from a C to T substitution at nucleotide position 487, causing the histidine (H) at amino acid position 163 to be replaced by a tyrosine (Y). 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	Benign	0.074
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.9
DANN	Benign	0.84
DEOGEN2	Benign	0.14	T;T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.42	T;.;.
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.086	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.8	L;L;L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.7	.;N;N
REVEL	Benign	0.098
Sift	Benign	0.33	.;T;T
Sift4G	Benign	0.59	T;T;T
Polyphen		0.59	P;P;P
Vest4		0.10
MutPred		0.50		Loss of disorder (P = 0.0892);Loss of disorder (P = 0.0892);Loss of disorder (P = 0.0892);
MVP		0.37
MPC		0.38
ClinPred		0.43	T
GERP RS		-2.2
Varity_R		0.043
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1951067454; hg19: chr11-102195727;