rs17725343

Positions:

• chr15-43409324-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014444.5(TUBGCP4):​c.*4110C>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 0.0223 in 587,522 control chromosomes in the GnomAD database, including 234 homozygotes. 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: 𝑓 0.019 (52 hom., cov: 32)
  • Exomes 𝑓: 0.023 (182 hom.)
• Consequence: TUBGCP4 NM_014444.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

Genes affected

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]

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]

TP53BP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0194 (2955/152338) while in subpopulation NFE AF= 0.0273 (1855/68036). AF 95% confidence interval is 0.0262. There are 52 homozygotes in gnomad4. There are 1418 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP4	NM_014444.5	c.*4110C>T		3_prime_UTR_variant	18/18	ENST00000564079.6	NP_055259.2
TP53BP1	NM_001141980.3	c.5401-228G>A		intron_variant		ENST00000382044.9	NP_001135452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBGCP4	ENST00000564079.6	c.*4110C>T		3_prime_UTR_variant	18/18	1	NM_014444.5	ENSP00000456648.2
TP53BP1	ENST00000382044.9	c.5401-228G>A		intron_variant		1	NM_001141980.3	ENSP00000371475.5

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2955 AN: 152220 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.00591

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0635

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0273

Gnomad OTH AF: 0.0268

GnomAD4 exome AF: 0.0233 AC: 10145 AN: 435184 Hom.: 182 Cov.: 4 AF XY: 0.0234 AC XY: 5347 AN XY: 228304

Gnomad4 AFR exome AF: 0.00547

Gnomad4 AMR exome AF: 0.0204

Gnomad4 ASJ exome AF: 0.0572

Gnomad4 EAS exome AF: 0.0000327

Gnomad4 SAS exome AF: 0.0199

Gnomad4 FIN exome AF: 0.0132

Gnomad4 NFE exome AF: 0.0267

Gnomad4 OTH exome AF: 0.0242

GnomAD4 genome AF: 0.0194 AC: 2955 AN: 152338 Hom.: 52 Cov.: 32 AF XY: 0.0190 AC XY: 1418 AN XY: 74494

Gnomad4 AFR AF: 0.00589

Gnomad4 AMR AF: 0.0216

Gnomad4 ASJ AF: 0.0635

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0174

Gnomad4 FIN AF: 0.0107

Gnomad4 NFE AF: 0.0273

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0257 Hom.: 18

Bravo AF: 0.0205

Asia WGS AF: 0.00606 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.74
DANN	Benign	0.50

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: rs17725343; hg19: chr15-43701522;