20-63236265-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39490348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIRC7	NM_139317.3	c.169G>T	p.Gly57Cys	missense_variant	Exon 1 of 7	ENST00000217169.8	NP_647478.1
BIRC7	NM_022161.4	c.169G>T	p.Gly57Cys	missense_variant	Exon 1 of 7		NP_071444.1
BIRC7	XM_047440495.1	c.-1671G>T		5_prime_UTR_variant	Exon 1 of 6		XP_047296451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIRC7	ENST00000217169.8	c.169G>T	p.Gly57Cys	missense_variant	Exon 1 of 7	1	NM_139317.3	ENSP00000217169.3
BIRC7	ENST00000342412.10	c.169G>T	p.Gly57Cys	missense_variant	Exon 1 of 7	1		ENSP00000345213.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.169G>T (p.G57C) alteration is located in exon 1 (coding exon 1) of the BIRC7 gene. This alteration results from a G to T substitution at nucleotide position 169, causing the glycine (G) at amino acid position 57 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.9	M;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.21
Sift	Uncertain	0.011	D;D
Sift4G	Benign	0.11	T;D
Polyphen		1.0	D;D
Vest4		0.32
MutPred		0.40		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP		0.63
MPC		0.53
ClinPred		0.95	D
GERP RS		3.8
Varity_R		0.30
gMVP		0.43

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-61867617; COSMIC: COSV53900939; COSMIC: COSV53900939;