20-37519060-C-G

Position:

• chr20-37519060-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006698.4(BLCAP):​c.115G>C​(p.Glu39Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BLCAP NM_006698.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.70

Genes affected

BLCAP (HGNC:1055): (BLCAP apoptosis inducing factor) This gene encodes a protein that reduces cell growth by stimulating apoptosis. Alternative splicing and the use of alternative promoters result in multiple transcript variants encoding the same protein. This gene is imprinted in brain where different transcript variants are expressed from each parental allele. Transcript variants initiating from the upstream promoter are expressed preferentially from the maternal allele, while transcript variants initiating downstream of the interspersed NNAT gene (GeneID:4826) are expressed from the paternal allele. Transcripts at this locus may also undergo A to I editing, resulting in amino acid changes at three positions in the N-terminus of the protein. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.779

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLCAP	NM_006698.4	c.115G>C	p.Glu39Gln	missense_variant	2/2	ENST00000373537.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLCAP	ENST00000373537.7	c.115G>C	p.Glu39Gln	missense_variant	2/2	1	NM_006698.4	P1

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 02, 2021

The c.115G>C (p.E39Q) alteration is located in exon 3 (coding exon 1) of the BLCAP gene. This alteration results from a G to C substitution at nucleotide position 115, causing the glutamic acid (E) at amino acid position 39 to be replaced by a glutamine (Q). 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	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;T;T;T;T;T;T;T;.;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.78	D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.11	T
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.4	N;.;N;N;N;N;N;N;D;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0050	D;.;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.016	D;.;D;D;D;D;D;.;.;D
Polyphen		1.0	D;D;D;D;D;D;D;D;.;.
Vest4		0.75
MutPred		0.65		Loss of ubiquitination at K41 (P = 0.0863);Loss of ubiquitination at K41 (P = 0.0863);Loss of ubiquitination at K41 (P = 0.0863);Loss of ubiquitination at K41 (P = 0.0863);Loss of ubiquitination at K41 (P = 0.0863);Loss of ubiquitination at K41 (P = 0.0863);Loss of ubiquitination at K41 (P = 0.0863);Loss of ubiquitination at K41 (P = 0.0863);Loss of ubiquitination at K41 (P = 0.0863);Loss of ubiquitination at K41 (P = 0.0863);
MVP		0.14
MPC		1.6
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.52
gMVP		0.89

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: chr20-36147462;