chr11-102324530-C-A

Variant names:

• chr11-102324530-C-A
• rs1279583232
• NM_001165.5:c.21C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001165.5(BIRC3):​c.21C>A​(p.Ser7Arg) 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. 13/22 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: 0.0460
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1572442).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC3	NM_001165.5	MANE Select	c.21C>A	p.Ser7Arg	missense	Exon 2 of 9	NP_001156.1	Q13489
	BIRC3	NM_182962.3		c.21C>A	p.Ser7Arg	missense	Exon 3 of 10	NP_892007.1	Q13489

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC3	ENST00000263464.9	TSL:1 MANE Select	c.21C>A	p.Ser7Arg	missense	Exon 2 of 9	ENSP00000263464.4	Q13489
	BIRC3	ENST00000673846.1		c.21C>A	p.Ser7Arg	missense	Exon 2 of 10	ENSP00000501181.1	A0A669KBC7
	BIRC3	ENST00000526421.6	TSL:2	c.21C>A	p.Ser7Arg	missense	Exon 3 of 10	ENSP00000501119.1	Q13489

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.086
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.046
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.24
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.13	T
Polyphen		0.96	D
Vest4		0.24
MutPred		0.43		Loss of disorder (P = 0.0843)
MVP		0.29
MPC		0.34
ClinPred		0.83	D
GERP RS		5.2
Varity_R		0.39
gMVP		0.60
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs1279583232; hg19: chr11-102195261;