NM_001168.3:c.425A>C

Variant names:

• chr17-78223550-A-C
• rs775321079
• NM_001168.3:c.425A>C

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.425A>C​(p.Asp142Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BIRC5 NM_001168.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20
• 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: 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=0.14935198).

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.425A>C	p.Asp142Ala	missense	Exon 4 of 4	NP_001159.2	A0A0B4J1S3
	BIRC5	NM_001012271.2		c.494A>C	p.Asp165Ala	missense	Exon 5 of 5	NP_001012271.1	H3BLT4
	BIRC5	NM_001012270.2		c.307A>C	p.Ile103Leu	missense	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.425A>C	p.Asp142Ala	missense	Exon 4 of 4	ENSP00000324180.4	A0A0B4J1S3
	BIRC5	ENST00000301633.8	TSL:1	c.494A>C	p.Asp165Ala	missense	Exon 5 of 5	ENSP00000301633.3	H3BLT4
	BIRC5	ENST00000374948.6	TSL:1	c.307A>C	p.Ile103Leu	missense	Exon 3 of 3	ENSP00000364086.1	O15392-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461520 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727008

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111820

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 33

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	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.91	T
PhyloP100		2.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.062
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.033	D
Vest4		0.094
MutPred		0.27		Gain of helix (P = 0.0325)
MVP		0.65
MPC		0.47
ClinPred		0.49	T
GERP RS		4.4
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
gMVP		0.57
Mutation Taster		=93/7	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: rs775321079; hg19: chr17-76219631;