chr17-78214392-C-T

Variant names:

• chr17-78214392-C-T
• rs267605071
• NM_001168.3:c.76C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001168.3(BIRC5):​c.76C>T​(p.Pro26Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P26T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BIRC5 NM_001168.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.58
• Publications: 2 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

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.76C>T	p.Pro26Ser	missense	Exon 1 of 4	NP_001159.2	A0A0B4J1S3
	BIRC5	NM_001012271.2		c.76C>T	p.Pro26Ser	missense	Exon 1 of 5	NP_001012271.1	H3BLT4
	BIRC5	NM_001012270.2		c.76C>T	p.Pro26Ser	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.76C>T	p.Pro26Ser	missense	Exon 1 of 4	ENSP00000324180.4	A0A0B4J1S3
	BIRC5	ENST00000301633.8	TSL:1	c.76C>T	p.Pro26Ser	missense	Exon 1 of 5	ENSP00000301633.3	H3BLT4
	BIRC5	ENST00000374948.6	TSL:1	c.76C>T	p.Pro26Ser	missense	Exon 1 of 3	ENSP00000364086.1	O15392-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447710 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 719580

African (AFR) AF: 0.00 AC: 0 AN: 32368

American (AMR) AF: 0.00 AC: 0 AN: 42968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25426

East Asian (EAS) AF: 0.00 AC: 0 AN: 38410

South Asian (SAS) AF: 0.00 AC: 0 AN: 85098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1105066

Other (OTH) AF: 0.00 AC: 0 AN: 59694

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Benign	0.69	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		6.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.79		Loss of phosphorylation at T21 (P = 0.1764)
MVP		0.64
MPC		1.1
ClinPred		1.0	D
GERP RS		4.2
PromoterAI		-0.016	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
gMVP		0.75

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: rs267605071; hg19: chr17-76210473; COSMIC: COSV56956329; COSMIC: COSV56956329;