NM_001168.3:c.23C>T

Variant names:

• chr17-78214339-C-T
• rs543367853
• NM_001168.3:c.23C>T

Variant summary

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

The NM_001168.3(BIRC5):​c.23C>T​(p.Pro8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,608,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BIRC5 NM_001168.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.271
• Publications: 0 publications found

Genes affected

BIRC5 (HGNC:593): (baculoviral IAP repeat containing 5) This gene is a member of the inhibitor of apoptosis (IAP) gene family, which encode negative regulatory proteins that prevent apoptotic cell death. IAP family members usually contain multiple baculovirus IAP repeat (BIR) domains, but this gene encodes proteins with only a single BIR domain. The encoded proteins also lack a C-terminus RING finger domain. Gene expression is high during fetal development and in most tumors, yet low in adult tissues. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

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=0.08481604).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168.3. 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
	BIRC5	NM_001168.3	MANE Select	c.23C>T	p.Pro8Leu	missense	Exon 1 of 4	NP_001159.2	A0A0B4J1S3
	BIRC5	NM_001012271.2		c.23C>T	p.Pro8Leu	missense	Exon 1 of 5	NP_001012271.1	H3BLT4
	BIRC5	NM_001012270.2		c.23C>T	p.Pro8Leu	missense	Exon 1 of 3	NP_001012270.1	O15392-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC5	ENST00000350051.8	TSL:1 MANE Select	c.23C>T	p.Pro8Leu	missense	Exon 1 of 4	ENSP00000324180.4	A0A0B4J1S3
	BIRC5	ENST00000301633.8	TSL:1	c.23C>T	p.Pro8Leu	missense	Exon 1 of 5	ENSP00000301633.3	H3BLT4
	BIRC5	ENST00000374948.6	TSL:1	c.23C>T	p.Pro8Leu	missense	Exon 1 of 3	ENSP00000364086.1	O15392-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152264 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000419 AC: 1 AN: 238680 AF XY: 0.00000768

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456512 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 724620

African (AFR) AF: 0.00 AC: 0 AN: 32842

American (AMR) AF: 0.00 AC: 0 AN: 44110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25922

East Asian (EAS) AF: 0.00 AC: 0 AN: 39034

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110078

Other (OTH) AF: 0.0000166 AC: 1 AN: 60104

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152382 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74516

African (AFR) AF: 0.00 AC: 0 AN: 41594

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

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	0.081
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.27
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.027
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.035	D
Polyphen		0.89	P
Vest4		0.24
MutPred		0.43		Loss of glycosylation at P8 (P = 0.009)
MVP		0.67
MPC		0.51
ClinPred		0.11	T
GERP RS		-0.54
PromoterAI		0.023	Neutral
gMVP		0.54
Mutation Taster		=87/13	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: rs543367853; hg19: chr17-76210420;