NM_001168.3:c.406G>A

Variant names:

• chr17-78223531-G-A
• rs2076529060
• NM_001168.3:c.406G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001168.3(BIRC5):​c.406G>A​(p.Glu136Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,613,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.000016 (0 hom.)
• Consequence: BIRC5 NM_001168.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.08
• 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]

ENSG00000308650 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2771913).
• BS2: High AC in GnomAdExome4 at 24 AD gene.

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.406G>A	p.Glu136Lys	missense	Exon 4 of 4	NP_001159.2	A0A0B4J1S3
	BIRC5	NM_001012271.2		c.475G>A	p.Glu159Lys	missense	Exon 5 of 5	NP_001012271.1	H3BLT4
	BIRC5	NM_001012270.2		c.288G>A	p.Ser96Ser	synonymous	Exon 3 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.406G>A	p.Glu136Lys	missense	Exon 4 of 4	ENSP00000324180.4	A0A0B4J1S3
	BIRC5	ENST00000301633.8	TSL:1	c.475G>A	p.Glu159Lys	missense	Exon 5 of 5	ENSP00000301633.3	H3BLT4
	BIRC5	ENST00000374948.6	TSL:1	c.288G>A	p.Ser96Ser	synonymous	Exon 3 of 3	ENSP00000364086.1	O15392-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461000 Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7 AN XY: 726708

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86032

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1111602

Other (OTH) AF: 0.0000166 AC: 1 AN: 60368

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74366

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.16
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.80	T
PhyloP100		5.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.15
Sift	Benign	0.13	T
Sift4G	Benign	0.53	T
Vest4		0.35
MutPred		0.43		Gain of methylation at E136 (P = 0.0121)
MVP		0.86
MPC		1.1
ClinPred		0.98	D
GERP RS		5.4
gMVP		0.65
Mutation Taster		=73/27	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: rs2076529060; hg19: chr17-76219612;