rs62431284

chr6-136261359-G-Cchr6-136261359-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_014739.3(BCLAF1):c.2663C>G(p.Thr888Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T888N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCLAF1 NM_014739.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.14

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, BCLAF1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCLAF1	NM_014739.3	c.2663C>G	p.Thr888Ser	missense_variant	12/13	ENST00000531224.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCLAF1	ENST00000531224.6	c.2663C>G	p.Thr888Ser	missense_variant	12/13	1	NM_014739.3	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
Cadd	Pathogenic	28
Dann	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;.;.;.;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T;T;T;T;T;.
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.59	D;D;D;D;D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.8	L;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.88	N;N;N;N;N;N
REVEL	Benign	0.27
Sift	Uncertain	0.014	D;D;D;D;D;D
Sift4G	Benign	0.095	T;T;T;T;T;T
Polyphen		1.0	D;D;.;P;D;D
Vest4		0.79
MutPred		0.11		Gain of MoRF binding (P = 0.1419);.;.;.;.;.;
MVP		0.50
ClinPred		0.59	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.036

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

Other links and lift over

dbSNP: rs62431284; hg19: chr6-136582497;