6-136268285-AGG-CGA

Variant names:

• chr6-136268285-AGG-CGA
• NM_014739.3:c.2272_2274delCCTinsTCG
• BCLAF1 p.Pro758Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_014739.3(BCLAF1):​c.2272_2274delCCTinsTCG​(p.Pro758Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P758T) 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: 8.04
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014739.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCLAF1	NM_014739.3	MANE Select	c.2272_2274delCCTinsTCG	p.Pro758Ser	missense	N/A	NP_055554.1	Q9NYF8-1
	BCLAF1	NM_001386700.1		c.2272_2274delCCTinsTCG	p.Pro758Ser	missense	N/A	NP_001373629.1	Q9NYF8-1
	BCLAF1	NM_001386701.1		c.2272_2274delCCTinsTCG	p.Pro758Ser	missense	N/A	NP_001373630.1	Q9NYF8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCLAF1	ENST00000531224.6	TSL:1 MANE Select	c.2272_2274delCCTinsTCG	p.Pro758Ser	missense	N/A	ENSP00000435210.1	Q9NYF8-1
	BCLAF1	ENST00000527759.5	TSL:1	c.2266_2268delCCTinsTCG	p.Pro756Ser	missense	N/A	ENSP00000434826.1	Q9NYF8-2
	BCLAF1	ENST00000530767.5	TSL:1	c.1753_1755delCCTinsTCG	p.Pro585Ser	missense	N/A	ENSP00000436501.1	Q9NYF8-4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-136589423;