6-136268273-A-T

Position:

• chr6-136268273-A-T

Variant summary

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

The NM_014739.3(BCLAF1):​c.2286T>A​(p.Ser762Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCLAF1 NM_014739.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52

Genes affected

BCLAF1 (HGNC:16863): (BCL2 associated transcription factor 1) This gene encodes a transcriptional repressor that interacts with several members of the BCL2 family of proteins. Overexpression of this protein induces apoptosis, which can be suppressed by co-expression of BCL2 proteins. The protein localizes to dot-like structures throughout the nucleus, and redistributes to a zone near the nuclear envelope in cells undergoing apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

BCLAF1 (HGNC:):

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
BCLAF1	NM_014739.3	c.2286T>A	p.Ser762Arg	missense_variant	10/13	ENST00000531224.6	NP_055554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCLAF1	ENST00000531224.6	c.2286T>A	p.Ser762Arg	missense_variant	10/13	1	NM_014739.3	ENSP00000435210.1

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

Oct 11, 2024

The c.2286T>A (p.S762R) alteration is located in exon 10 (coding exon 8) of the BCLAF1 gene. This alteration results from a T to A substitution at nucleotide position 2286, causing the serine (S) at amino acid position 762 to be replaced by an arginine (R). 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	0.87
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;.;.;.;.;.
Eigen	Benign	0.068
Eigen_PC	Benign	0.072
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;.
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.24	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;.;.;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.54	N;N;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.076	T;D;D;T;T;D
Sift4G	Benign	0.35	T;T;T;T;T;T
Polyphen		0.94	P;P;.;D;P;P
Vest4		0.45
MutPred		0.28		Loss of phosphorylation at S762 (P = 0);.;Loss of phosphorylation at S762 (P = 0);.;.;.;
MVP		0.28
ClinPred		0.53	D
GERP RS		2.4
Varity_R		0.081
gMVP		0.093

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.31		Position offset: 0

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: chr6-136589411;