17-42823763-T-G

Position:

• chr17-42823763-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000590099.6(BECN1):​c.115A>C​(p.Ile39Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: BECN1 ENST00000590099.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.47

Genes affected

BECN1 (HGNC:1034): (beclin 1) This gene encodes a protein that regulates autophagy, a catabolic process of degradation induced by starvation. The encoded protein is a component of the phosphatidylinositol-3-kinase (PI3K) complex which mediates vesicle-trafficking processes. This protein is thought to play a role in multiple cellular processes, including tumorigenesis, neurodegeneration and apoptosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

ACMG classification

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=0.159989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BECN1	NM_001313998.2	c.115A>C	p.Ile39Leu	missense_variant	2/12	ENST00000590099.6	NP_001300927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BECN1	ENST00000590099.6	c.115A>C	p.Ile39Leu	missense_variant	2/12	1	NM_001313998.2	ENSP00000465364	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jun 13, 2024

The c.115A>C (p.I39L) alteration is located in exon 2 (coding exon 1) of the BECN1 gene. This alteration results from a A to C substitution at nucleotide position 115, causing the isoleucine (I) at amino acid position 39 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	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Benign	0.86
DEOGEN2	Benign	0.11	T;T;T;.;T
Eigen	Benign	-0.22
Eigen_PC	Benign	0.021
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.92	.;D;D;D;D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.16	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.64	N;N;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.13	N;.;N;.;.
REVEL	Benign	0.073
Sift	Benign	0.84	T;.;T;.;.
Sift4G	Benign	1.0	T;T;T;.;.
Polyphen		0.0	B;B;B;.;.
Vest4		0.36
MutPred		0.36		Loss of catalytic residue at I39 (P = 0.006);Loss of catalytic residue at I39 (P = 0.006);Loss of catalytic residue at I39 (P = 0.006);Loss of catalytic residue at I39 (P = 0.006);Loss of catalytic residue at I39 (P = 0.006);
MVP		0.33
MPC		0.45
ClinPred		0.65	D
GERP RS		5.3
Varity_R		0.14
gMVP		0.50

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: chr17-40975781;