2-32357420-A-T

Position:

• chr2-32357420-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016252.4(BIRC6):​c.259A>T​(p.Ser87Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BIRC6 NM_016252.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.14

Genes affected

BIRC6 (HGNC:13516): (baculoviral IAP repeat containing 6) This gene encodes a protein with a BIR (baculoviral inhibition of apoptosis protein repeat) domain and a UBCc (ubiquitin-conjugating enzyme E2, catalytic) domain. This protein inhibits apoptosis by facilitating the degradation of apoptotic proteins by ubiquitination. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIRC6	NM_016252.4	c.259A>T	p.Ser87Cys	missense_variant	1/74	ENST00000421745.7	NP_057336.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIRC6	ENST00000421745.7	c.259A>T	p.Ser87Cys	missense_variant	1/74	1	NM_016252.4	ENSP00000393596.2
BIRC6	ENST00000700518.1	c.259A>T	p.Ser87Cys	missense_variant	1/73			ENSP00000515025.1
BIRC6	ENST00000700519.1	c.259A>T	p.Ser87Cys	missense_variant	1/74			ENSP00000515026.1
BIRC6	ENST00000648282.1	c.94A>T	p.Ser32Cys	missense_variant	1/58			ENSP00000498175.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2024

The c.259A>T (p.S87C) alteration is located in exon 1 (coding exon 1) of the BIRC6 gene. This alteration results from a A to T substitution at nucleotide position 259, causing the serine (S) at amino acid position 87 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	0.10
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Benign	0.96
Eigen	Benign	-0.0029
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.65	D
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.46	T
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.32
Sift	Benign	0.075	T
Sift4G	Uncertain	0.0090	D
Vest4		0.31
MutPred		0.78		Loss of loop (P = 0.0603);
MVP		0.61
MPC		1.5
ClinPred		0.72	D
GERP RS		4.0
gMVP		0.60

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: chr2-32582488;