Variant chr15-43376032-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.203

Variant links:

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]

TUBGCP4 links:

TUBGCP4 (HGNC:):

TUBGCP4 links:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP4	NM_014444.5 linkuse as main transcript	c.79-66G>A		intron_variant		ENST00000564079.6	NP_055259.2	Q9UGJ1-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
TUBGCP4	ENST00000564079.6 linkuse as main transcript	c.79-66G>A	intron_variant	1	NM_014444.5	ENSP00000456648.2	Q9UGJ1-2
TUBGCP4	ENST00000260383.11 linkuse as main transcript	c.79-66G>A	intron_variant	1		ENSP00000260383.7	Q9UGJ1-1
TUBGCP4	ENST00000563517.5 linkuse as main transcript	n.79-66G>A	intron_variant	5		ENSP00000454696.1	H3BN56
TUBGCP4	ENST00000570081.1 linkuse as main transcript	n.294-66G>A	intron_variant	4

Frequencies

GnomAD3 genomes

AF:

0.00428

AC:

652

AN:

152174

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.000363

AC XY:

260

AN XY:

716046

show subpopulations

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.:

Cov.:

AF XY:

0.00395

AC XY:

294

AN XY:

74458

show subpopulations

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.:

Bravo

AF:

0.00521

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over