NM_139317.3:c.169G>T

Variant names:

• chr20-63236265-G-T
• NM_139317.3:c.169G>T

Variant summary

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

The NM_139317.3(BIRC7):​c.169G>T​(p.Gly57Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BIRC7 NM_139317.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52
• Publications: 0 publications found

Genes affected

BIRC7 (HGNC:13702): (baculoviral IAP repeat containing 7) This gene encodes a member of the inhibitor of apoptosis protein (IAP) family, and contains a single copy of a baculovirus IAP repeat (BIR) as well as a RING-type zinc finger domain. The BIR domain is essential for inhibitory activity and interacts with caspases, while the RING finger domain sometimes enhances antiapoptotic activity but does not inhibit apoptosis alone. Elevated levels of the encoded protein may be associated with cancer progression and play a role in chemotherapy sensitivity. Alternative splicing results in multiple transcript variants [provided by RefSeq, Jul 2013]

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=0.39490348).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139317.3. 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
	BIRC7	NM_139317.3	MANE Select	c.169G>T	p.Gly57Cys	missense	Exon 1 of 7	NP_647478.1	Q96CA5-1
	BIRC7	NM_022161.4		c.169G>T	p.Gly57Cys	missense	Exon 1 of 7	NP_071444.1	Q96CA5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC7	ENST00000217169.8	TSL:1 MANE Select	c.169G>T	p.Gly57Cys	missense	Exon 1 of 7	ENSP00000217169.3	Q96CA5-1
	BIRC7	ENST00000342412.10	TSL:1	c.169G>T	p.Gly57Cys	missense	Exon 1 of 7	ENSP00000345213.6	Q96CA5-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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	0.28
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.9	M
PhyloP100		2.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.21
Sift	Uncertain	0.011	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.32
MutPred		0.40		Gain of sheet (P = 0.0266)
MVP		0.63
MPC		0.53
ClinPred		0.95	D
GERP RS		3.8
PromoterAI		0.016	Neutral
Varity_R		0.30
gMVP		0.43
Mutation Taster		=84/16	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: chr20-61867617; COSMIC: COSV53900939; COSMIC: COSV53900939;