Variant chr2-32401533-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016252.4(BIRC6):c.1328C>T(p.Pro443Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

BIRC6
NM_016252.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.02

Variant links:

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]

BIRC6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12023404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIRC6	NM_016252.4 linkuse as main transcript	c.1328C>T	p.Pro443Leu	missense_variant	8/74	ENST00000421745.7	NP_057336.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
BIRC6	ENST00000421745.7 linkuse as main transcript	c.1328C>T	p.Pro443Leu	missense_variant	8/74	1	NM_016252.4	ENSP00000393596	P2
BIRC6	ENST00000700518.1 linkuse as main transcript	c.1328C>T	p.Pro443Leu	missense_variant	8/73			ENSP00000515025	A2
BIRC6	ENST00000700519.1 linkuse as main transcript	c.1328C>T	p.Pro443Leu	missense_variant	8/74			ENSP00000515026
BIRC6	ENST00000648282.1 linkuse as main transcript	c.1166C>T	p.Pro389Leu	missense_variant	8/58			ENSP00000498175

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461684

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2022

The c.1328C>T (p.P443L) alteration is located in exon 8 (coding exon 8) of the BIRC6 gene. This alteration results from a C to T substitution at nucleotide position 1328, causing the proline (P) at amino acid position 443 to be replaced by a leucine (L). 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

0.068

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

0.020

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.97

M_CAP

Benign

0.0097

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.079

Sift

Uncertain

0.013

Sift4G

Uncertain

0.015

Vest4

0.20

MutPred

0.39

Loss of disorder (P = 0.0512);

MVP

0.50

MPC

0.18

ClinPred

0.80

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

gMVP

0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over