11-102324562-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001165.5(BIRC3):c.53A>G(p.Asn18Ser) 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 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: not found (cov: 32)
• Consequence: BIRC3 NM_001165.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.604

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052036107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIRC3	NM_001165.5	c.53A>G	p.Asn18Ser	missense_variant	2/9	ENST00000263464.9
BIRC3	NM_182962.3	c.53A>G	p.Asn18Ser	missense_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIRC3	ENST00000263464.9	c.53A>G	p.Asn18Ser	missense_variant	2/9	1	NM_001165.5	P1
	ENST00000673690.1	n.96-1790T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

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

Mar 07, 2024

The c.53A>G (p.N18S) alteration is located in exon 1 (coding exon 1) of the BIRC3 gene. This alteration results from a A to G substitution at nucleotide position 53, causing the asparagine (N) at amino acid position 18 to be replaced by a serine (S). 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	0.062
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.1
Dann	Benign	0.38
DEOGEN2	Benign	0.067	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.62	T;.;.
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.052	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N;N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.85	T;T;T
Polyphen		0.0040	B;B;B
Vest4		0.025
MutPred		0.32		Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);
MVP		0.18
MPC		0.21
ClinPred		0.084	T
GERP RS		-0.14
Varity_R		0.045
gMVP		0.075

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: rs1197601579; hg19: chr11-102195293;