15-43469997-CC-GA

Variant names:

• chr15-43469997-CC-GA
• NM_001141980.3:c.1249_1250delGGinsTC
• TP53BP1 p.Gly417Ser

Variant summary

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

The NM_001141980.3(TP53BP1):​c.1249_1250delGGinsTC​(p.Gly417Ser) variant causes a missense change involving the alteration of a non-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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TP53BP1 NM_001141980.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 0 publications found

Genes affected

TP53BP1 (HGNC:11999): (tumor protein p53 binding protein 1) This gene encodes a protein that functions in the DNA double-strand break repair pathway choice, promoting non-homologous end joining (NHEJ) pathways, and limiting homologous recombination. This protein plays multiple roles in the DNA damage response, including promoting checkpoint signaling following DNA damage, acting as a scaffold for recruitment of DNA damage response proteins to damaged chromatin, and promoting NHEJ pathways by limiting end resection following a double-strand break. These roles are also important during V(D)J recombination, class switch recombination and at unprotected telomeres. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141980.3. 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
	TP53BP1	NM_001141980.3	MANE Select	c.1249_1250delGGinsTC	p.Gly417Ser	missense	N/A	NP_001135452.1	Q12888-2
	TP53BP1	NM_001141979.3		c.1249_1250delGGinsTC	p.Gly417Ser	missense	N/A	NP_001135451.1	Q12888-3
	TP53BP1	NM_005657.4		c.1234_1235delGGinsTC	p.Gly412Ser	missense	N/A	NP_005648.1	Q12888-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53BP1	ENST00000382044.9	TSL:1 MANE Select	c.1249_1250delGGinsTC	p.Gly417Ser	missense	N/A	ENSP00000371475.5	Q12888-2
	TP53BP1	ENST00000450115.6	TSL:1	c.1249_1250delGGinsTC	p.Gly417Ser	missense	N/A	ENSP00000393497.2	Q12888-3
	TP53BP1	ENST00000263801.7	TSL:1	c.1234_1235delGGinsTC	p.Gly412Ser	missense	N/A	ENSP00000263801.3	Q12888-1

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		1.4

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: chr15-43762195;