rs999047

chr15-43396718-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014444.5(TUBGCP4):c.1172-496A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,050 control chromosomes in the GnomAD database, including 10,048 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 0.29 (10048 hom., cov: 32)
• Consequence: TUBGCP4 NM_014444.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.768

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBGCP4	NM_014444.5	c.1172-496A>G		intron_variant		ENST00000564079.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBGCP4	ENST00000564079.6	c.1172-496A>G		intron_variant		1	NM_014444.5	A1
TUBGCP4	ENST00000260383.11	c.1172-496A>G		intron_variant		1		P4
TUBGCP4	ENST00000561691.5	c.928-496A>G		intron_variant, NMD_transcript_variant		1
TUBGCP4	ENST00000563963.1	n.1609-496A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44236 AN: 151932 Hom.: 10012 Cov.: 32

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.292 AC: 44330 AN: 152050 Hom.: 10048 Cov.: 32 AF XY: 0.288 AC XY: 21381 AN XY: 74332

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.253

Alfa AF: 0.163 Hom.: 3913

Bravo AF: 0.321

Asia WGS AF: 0.370 AC: 1286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.099
Dann	Benign	0.52

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: rs999047; hg19: chr15-43688916;