NM_001141980.3:c.*3705C>T

Variant names:

• chr15-43403678-G-A
• rs762108781
• NM_001141980.3:c.*3705C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001141980.3(TP53BP1):​c.*3705C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000894 in 1,454,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: TP53BP1 NM_001141980.3 3_prime_UTR
• Scores: Splicing: ADA: 0.9949
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.617

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]

TUBGCP4 (HGNC:16691): (tubulin gamma complex component 4) This gene encodes a component of the gamma-tubulin ring complex, which is required for microtubule nucleation. In mammalian cells, the protein localizes to centrosomes in association with gamma-tubulin. Crystal structure analysis revealed a structure composed of five helical bundles arranged around conserved hydrophobic cores. An exposed surface area located in the C-terminal domain is essential and sufficient for direct binding to gamma-tubulin. Mutations in this gene that alter microtubule organization are associated with microcephaly and chorioretinopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 15-43403678-G-A is Benign according to our data. Variant chr15-43403678-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1036151.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53BP1	NM_001141980.3	c.*3705C>T		3_prime_UTR_variant	Exon 28 of 28	ENST00000382044.9	NP_001135452.1
TUBGCP4	NM_014444.5	c.1732-5G>A		splice_region_variant, intron_variant	Intron 15 of 17	ENST00000564079.6	NP_055259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53BP1	ENST00000382044	c.*3705C>T		3_prime_UTR_variant	Exon 28 of 28	1	NM_001141980.3	ENSP00000371475.5
TUBGCP4	ENST00000564079.6	c.1732-5G>A		splice_region_variant, intron_variant	Intron 15 of 17	1	NM_014444.5	ENSP00000456648.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000443 AC: 11 AN: 248558 Hom.: 0 AF XY: 0.0000297 AC XY: 4 AN XY: 134844

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000321

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000894 AC: 13 AN: 1454326 Hom.: 0 Cov.: 28 AF XY: 0.00000829 AC XY: 6 AN XY: 723856

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000269

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 22, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.78
SpliceAI score (max)		0.16		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: rs762108781; hg19: chr15-43695876;