15-43376032-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014444.5(TUBGCP4):c.79-66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000795 in 1,595,804 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00043 (6 hom.)
• Consequence: TUBGCP4 NM_014444.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.203

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-43376032-G-A is Benign according to our data. Variant chr15-43376032-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1180892.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00428 (652/152292) while in subpopulation AFR AF= 0.0148 (616/41566). AF 95% confidence interval is 0.0139. There are 4 homozygotes in gnomad4. There are 294 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBGCP4	NM_014444.5	c.79-66G>A		intron_variant		ENST00000564079.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBGCP4	ENST00000564079.6	c.79-66G>A		intron_variant		1	NM_014444.5	A1
TUBGCP4	ENST00000260383.11	c.79-66G>A		intron_variant		1		P4
TUBGCP4	ENST00000563517.5	c.79-66G>A		intron_variant, NMD_transcript_variant		5
TUBGCP4	ENST00000570081.1	n.294-66G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00428 AC: 652 AN: 152174 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.000427 AC: 617 AN: 1443512 Hom.: 6 AF XY: 0.000363 AC XY: 260 AN XY: 716046

Gnomad4 AFR exome AF: 0.0159

Gnomad4 AMR exome AF: 0.000744

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000772

Gnomad4 SAS exome AF: 0.0000821

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000818

Gnomad4 OTH exome AF: 0.000622

GnomAD4 genome AF: 0.00428 AC: 652 AN: 152292 Hom.: 4 Cov.: 32 AF XY: 0.00395 AC XY: 294 AN XY: 74458

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00291 Hom.: 0

Bravo AF: 0.00521

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.3
Dann	Benign	0.84

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: rs142688668; hg19: chr15-43668230;