chr2-32377717-C-A

Variant names:

• chr2-32377717-C-A
• NM_016252.4:c.455C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016252.4(BIRC6):​c.455C>A​(p.Thr152Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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: BIRC6 NM_016252.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.04
• Publications: 0 publications found

Genes affected

BIRC6 (HGNC:13516): (baculoviral IAP repeat containing 6) This gene encodes a protein with a BIR (baculoviral inhibition of apoptosis protein repeat) domain and a UBCc (ubiquitin-conjugating enzyme E2, catalytic) domain. This protein inhibits apoptosis by facilitating the degradation of apoptotic proteins by ubiquitination. [provided by RefSeq, Jul 2008]

BIRC6-AS1 (HGNC:40641): (BIRC6 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34618366).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016252.4. 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
	BIRC6	NM_016252.4	MANE Select	c.455C>A	p.Thr152Asn	missense	Exon 2 of 74	NP_057336.3	Q9NR09
	BIRC6	NM_001378125.1		c.371C>A	p.Thr124Asn	missense	Exon 2 of 74	NP_001365054.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC6	ENST00000421745.7	TSL:1 MANE Select	c.455C>A	p.Thr152Asn	missense	Exon 2 of 74	ENSP00000393596.2	Q9NR09
	BIRC6	ENST00000700518.1		c.455C>A	p.Thr152Asn	missense	Exon 2 of 73	ENSP00000515025.1	A0A8V8TQB4
	BIRC6	ENST00000700519.1		c.455C>A	p.Thr152Asn	missense	Exon 2 of 74	ENSP00000515026.1	A0A8V8TR92

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	Benign	0.21
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	0.98
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.54	T
PhyloP100		6.0
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.23
Sift	Benign	0.060	T
Sift4G	Benign	0.15	T
Vest4		0.45
MutPred		0.25		Gain of catalytic residue at T152 (P = 0.0714)
MVP		0.59
MPC		1.8
ClinPred		0.96	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.27
Mutation Taster		=90/10	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

hg19: chr2-32602785;